ORCID Profile
0000-0002-9789-245X
Current Organisation
Tokai Daigaku Igakubu
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Publisher: Asian Australasian Association of Animal Production Societies
Date: 11-2021
DOI: 10.5713/AB.20.0763
Abstract: Objective: Microminipig (MMP) is a miniature pig with an extra small body size for experimental use. In the present study, the occurrence of stillbirths and their genetic association with swine leukocyte antigen (SLA) class II haplotypes were evaluated in a population of MMPs.Methods: The occurrences of stillbirth and genetic association with SLA class II haplotypes using 483 stillborn and 2,246 live piglets, and their parents were compared among the three groups of newborn piglet litters an all stillborn (AS) group consisting of only stillborn piglet litters, a partial stillborn (PS) group consisting of stillborn and live piglet litters, and an all alive (AA) group consisting of only live piglet litters.Results: The incidence of stillborn piglets was 483/2,729 (17.7%). Distributions of litter sizes, numbers of stillborn piglets in a litter, parities, and gestation periods were distinct among the three groups. The frequencies of low resolution haplotype (Lr)-0.7 or Lr-0.23 were higher in the AS group than in the PS or AA groups. In sires, the frequency of Lr-0.7 associated with the AS group was significantly higher in the AS group than with the AA group. In dams, the frequency of Lr-0.23 was significantly higher in the AS group than in the PS or AA groups, whereas the frequency of Lr-0.7 was not significantly different.Conclusion: The incidence of stillborn piglets in MMPs appears to be higher than those in other pig breeds. Several traits related with stillbirths such as the number of stillborn piglets and parities of the AS group were different from those of the PS and AA groups. Specific SLA class II haplotypes were associated significantly with a high incidence of stillbirths and could be used as genetic markers to adopt breeding strategies to lower the rate of stillbirth in MMPs.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2004
DOI: 10.1111/J.1601-5223.1997.00037.X
Abstract: The PERB11 gene family has at least five members within the telomeric region of the MHC. The PERB11.1 and PERB11.2 genes are approximately 40 kb and 160 kb centromeric of HLA-B, respectively. Using continuous genomic sequence encompassing PERB11.1 and PERB11.2, we have found a large (approximately 25 kb) segmental duplication extending beyond the genes themselves and other potential coding sequences. The major difference between the segments are large indels which are predominantly Alu sequences. The Alu sequences within the duplicated segments have created ersity via the internal and 3' poly A-rich region. A sequence comparison of an Alu sequence between two different human ancestral haplotypes shows a high level of polymorphism, particularly in the poly A-rich regions. This study characterises the Alu sequences within the peri-PERB11.1 and peri-PERB11.2 duplicated segments in relation to ersity and polymorphism and as evolutionary markers.
Publisher: Springer Science and Business Media LLC
Date: 06-1999
DOI: 10.1007/PL00006511
Abstract: Sixteen human endogenous retrovirus (HERV) sequences were detected within 656 kb of genomic sequence obtained from the alpha- and beta-block of the class I region of the major histocompatibility complex (MHC). The HERVs were identified and characterized as family members of HERV-16 (11 copies), HERV-L (1 copy), HERV-I (2 copies), HERV-K91 (1 copy), and HARLEQUIN (1 copy) by sequence comparison using CENSOR or Repeat Masker, BLAST searches, and dot plots. The 11 copies of HERV-16 arose as products of duplication of genomic segments containing HLA class I (HLAcI) and PERB11 (MIC) genes inter alia, whereas the other five HERVs arose after duplication probably as a consequence of single insertion events or translocations. HERV-L and HERV-I are located between the duplicated genes PERB11.2 (MICB) and PERB11.1 (MICA), and HLA-B and HLA-C, respectively, whereas HERV-K91 and HARLEQUIN are located telomeric of HLA-C. A highly fragmented copy of HERV-I was also found telomeric of PERB11. 4. Structural analysis of open reading frames (ORFs) revealed the absence of intact coding sequence within the putative gag, pol, and env gene regions of all the HERVs with the exception of HERV-K91, which had two large ORFs within the region of the putative protease and pol genes. In addition, the 5'-LTR of HERV-L contained a 2.5-kb element that was AT-rich and large ORFs with putative amino acid sequences rich in tyrosines and isoleucines. HERV-I, HARLEQUIN, and at least four copies of HERV-16 appear to have been receptors for the insertion of other retrotransposons including Alu elements and fragments of L1 and THE1. Examination of flanking sequences suggests that HERV-I and HERV-L had occurred by insertion into ancient L1 fragments. This study has revealed that the alpha- and beta-block region within the MHC is rich in HERV sequences occurring at a much higher ratio (10 to 1) than normally observed in the human genome. These HERV sequences will therefore enhance further studies on disease associations and differences between human haplotypes and primates and their role in the evolution of class I genes in the MHC.
Publisher: Oxford University Press (OUP)
Date: 06-07-2005
DOI: 10.1093/HMG/DDI234
Abstract: A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to in idual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.
Publisher: Ornithological Society of Japan
Date: 07-04-2021
DOI: 10.2326/OSJ.20.93
Publisher: Elsevier BV
Date: 11-1983
DOI: 10.1016/S0006-291X(83)80240-X
Abstract: Fetal calf serum (20%) does not substitute for insulin in terms of enhanced accumulation of rat casein mRNAs, but it can sustain the mammary tissue in culture. This property of fetal calf serum was utilized to show that in the presence of cortisol and 1) insulin or 2) prolactin, the delayed addition of prolactin or insulin, respectively, produced similar enhancement of 25 K and 42 K casein mRNAs. The results indicate that both insulin and prolactin are required for accumulation of rat casein mRNAs, the accumulation is independent of the sequence of addition of these hormones, and that the response cannot be ascribed entirely to the hormone added last.
Publisher: Springer Science and Business Media LLC
Date: 06-1998
DOI: 10.1007/PL00006355
Abstract: One of the most important factors affecting the increase of clients' satisfaction is how health care providers (HCP) communicate with clients. On the other hand, different factors can hinder proper communication and thus education, which is one of the main tasks of HCP. Therefore, the purpose of this study was to investigate communication barriers to education to referrals from the perspective of referrals to health centers (RHC) and HCP. This descriptive-analytical study was conducted on RHC and HCP in Kerman in 2021. Using a multi-stage s ling method, 162 HCP and 414 RHC were included in the study. The data collection tool was two researcher-made questionnaires. Data were analyzed using SPSS 16. From the perspective of RHC and HCP, most communication barriers were related to environmental and then socio-cultural factors. Among the demographic variables of HCP, level of education showed a significant relationship with the physical-psychological, verbal-non-verbal, and informational domains. And in relation to RHC, a significant relationship was found between education and job in the socio-cultural field and environmental barriers ( HCP face a variety of barriers in educating people, most of which are related to environmental factors. Given the cost-effectiveness of education to the public, it is essential that planners and policymakers use strategies to eliminate environmental factors as well as the placement of indigenous HCP in health facilities to reduce communication barriers.
Publisher: Oxford University Press (OUP)
Date: 09-2008
DOI: 10.1534/GENETICS.108.090340
Abstract: The frequency and HLA-A allelic associations of a HERVK9 DNA structural polymorphism located in close proximity to the highly polymorphic HLA-A gene within the major histocompatibility complex (MHC) genomic region were determined in Japanese, African Americans, and Australian Caucasians to better understand its human population evolutionary history. The HERVK9 insertion or deletion was detected as a 3′ LTR or a solo LTR, respectively, by separate PCR assays. The average insertion frequency of the HERVK9.HG was significantly different (P & 1.083e−6) between the Japanese (0.59) and the African Americans (0.34) or Australian Caucasians (0.37). LD analysis predicted a highly significant (P & 1.0e−5) linkage between the HLA-A and HERVK9 alleles, probably as a result of hitchhiking (linkage). Evolutionary time estimates of the solo, 5′ and 3′ LTR nucleotide sequence ergences suggest that the HERVK9 was inserted 17.3 MYA with the first structural deletion occurring 15.1 MYA. The LTR/HLA-A haplotypes appear to have been formed mostly during the past 3.9 MY. The HERVK9 insertion and deletion, detected by a simple and economical PCR method, is an informative genetic and evolutionary marker for the study of HLA-A haplotype variations, human migration, the origins of contemporary populations, and the possibility of disease associations.
Publisher: Frontiers Media SA
Date: 07-07-2021
DOI: 10.3389/FGENE.2021.636236
Abstract: The analysis of polymorphic variations in the human major histocompatibility complex (MHC) class II genomic region on the short-arm of chromosome 6 is a scientific enquiry to better understand the ersity in population structure and the effects of evolutionary processes such as recombination, mutation, genetic drift, demographic history, and natural selection. In order to investigate associations between the polymorphisms of HLA-DRB1 gene and recent Alu insertions (POALINs) in the HLA class II region, we genotyped HLA-DRB1 and five Alu loci (AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10), and determined their allele frequencies and haplotypic associations in 12 minority ethnic populations in China. There were 42 different HLA-DRB1 alleles for ethnic Chinese ranging from 12 alleles in the Jinuo to 28 in the Yugur with only DRB1 ∗ 08:03, DRB1 ∗ 09:01, DRB1 ∗ 12:02, DRB1 ∗ 14:01, DRB1 ∗ 15:01, and DRB1 ∗ 15:02 present in all ethnic groups. The POALINs varied in frequency between 0.279 and 0.514 for AluDPB2, 0 and 0.127 for AluDQA2, 0.777 and 0.995 for AluDQA1, 0.1 and 0.455 for AluDRB1 and 0.084 and 0.368 for AluORF10. By comparing the data of the five-loci POALIN in 13 Chinese ethnic populations (including Han-Yunnan published data) against Japanese and Caucasian published data, marked differences were observed between the populations at the allelic or haplotypic levels. Five POALIN loci were in significant linkage disequilibrium with HLA-DRB1 in different populations and AluDQA1 had the highest percentage association with most of the HLA-DRB1 alleles, whereas the nearby AluDRB1 indel was strongly haplotypic for only DRB1 ∗ 01, DRB1 ∗ 10, DRB1 ∗ 15 and DRB1 ∗ 16. There were 30 five-locus POALIN haplotypes inferred in all populations with H5 (no Alu insertions except for AluDQA1) and H21 (only AluDPB2 and AluDQA1 insertions) as the two predominant haplotypes. Neighbor joining trees and principal component analyses of the Alu and HLA-DRB1 polymorphisms showed that genetic ersity of these genomic markers is associated strongly with the population characteristics of language family, migration and sociality. This comparative study of HLA-DRB1 alleles and multilocus, lineage POALIN frequencies of Chinese ethnic populations confirmed that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic and evolutionary markers for the identification of allele and haplotype lineages and genetic variations within the same and/or different populations.
Publisher: Proceedings of the National Academy of Sciences
Date: 10-06-2003
Abstract: Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other (≈6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.
Publisher: Elsevier BV
Date: 09-1989
DOI: 10.1016/0166-0934(89)90059-1
Abstract: The potential of using a chemically synthesized oligodeoxynucleotide as a diagnostic probe to detect human papillomavirus type 16 (HPV-16) in genital infections was evaluated by comparing it with a cloned full-length HPV-16 probe in dot-blot DNA hybridizations. An oligonucleotide sequence, 20 bases in length from the E6 region of HPV-16 (E6 oligo) and different from the DNA sequences of HPV types 6, 11 and 18 by at least 2 base pairs, was chosen for chemical synthesis. The oligoprobe, which was 5'-end labelled with [32P]dATP, was found to be specific, but approximately ten times less sensitive than the full-length radiolabelled probe of HPV-16, in dot-blot hybridizations with the DNA of HPV-6, -11, -16 and -18, HPV positive and negative cell-lines. From 36 cervical or vulval scrapes two s les were found positive with both cloned HPV-16 and oligoprobe hybridization. Of 21 s les of formalin-fixed, paraffin-embedded squamous cell carcinomas originating from anus, oesophagus, penis, colon, breast and skin only 4 anal squamous cell carcinomas were positives when hybridized with cloned HPV-16 DNA or with the oligoprobe. This study confirms that HPV-16, which is frequently associated with squamous cell carcinoma of the cervix is also strongly associated with squamous cell carcinoma of the anus.
Publisher: Wiley
Date: 08-2003
Abstract: Most Alu members of the large SINE family are fixed within the human genome but some younger mobile members are dimorphic, that is, they are either present or absent in the genome. Four different dimorphic Alu insertions have been identified and characterized previously within the class I region of the major histocompatibility complex (MHC). Here we report on (i) the identification and characterization of a new dimorphic Alu insertion, AluyTF, located between the transcription factor II H (TFIIH) and corneodesmosin (CDSN) genes within a region of the MHC that is telomeric of the human leukocyte antigen type B (HLA-B) locus and centromeric of the HLA-A locus, (ii) the haplotypic relationships between the AluyTF dimorphism and the HLA-A and -B loci within a panel of 48 IHW cell-lines representing at least 36 different HLA class I haplotypes, (iii) the AluyTF genotype, allele and haplotype frequencies present in the Australian caucasian and Japanese populations, and (iv) the frequency of association between the AluTF dimorphisms and HLA-A and -B alleles in 108 Australian caucasians and 99 Japanese. The AluyTF insertion was present at 27% in the IHW cell lines, and the gene frequency was 0.107 and 0.083 in the Australian caucasian and Japanese population, respectively. The Alu haplotype frequencies constructed from four different dimorphic Alu loci including AluyTF within the MHC were not significantly different (p > 0.05) between the two populations. There were no significant associations between the Alu insertion and either the HLA-A or -B alleles except for a moderately strong association with HLA-A29 in the Australians (71.7%). This polymorphic AluyTF element, along with the four other previously described polymorphic Alu elements within the class I region of the MHC, will be useful lineage and linkage markers in human population studies and for elucidating the evolution of HLA class I haplotypes.
Publisher: Springer Science and Business Media LLC
Date: 12-2001
Abstract: The human CD1 proteins belong to a lipid-glycolipid antigen-presenting gene family and are related in structure and function to the MHC class I molecules. Previous mapping and DNA hybridization studies have shown that five linked genes located within a cluster on human chromosome 1q22-23 encode the CD1 protein family. We have analyzed the complete genomic sequence of the human CD1 gene cluster and found that the five active genes are distributed over 175,600 nucleotides and separated by four expanded intervening genomic regions (IGRs) ranging in length between 20 and 68 kb. The IGRs are composed mostly of retroelements including five full-length L1 PA sequences and various pseudogenes. Some L1 sequences have acted as receptors for other subtypes or families of retroelements. Alu molecular clocks that have evolved during primate history are found distributed within the HLA class I duplicated segments (duplicons) but not within the duplicons of CD1. Phylogeny of the alpha3 domain of the class I-like superfamily of proteins shows that the CD1 cluster is well separated from HLA class I by a number of superfamily members including MIC (PERB11), HFE, Zn-alpha2-GP, FcRn, and MR1. Phylogenetically, the human CD1 sequences are interspersed by CD1 sequences from other mammalian species, whereas the human HLA class I sequences cluster together and are separated from the other mammalian sequences. Genomic and phylogenetic analyses support the view that the human CD1 gene copies were duplicated prior to the evolution of primates and the bulk of the HLA class I genes found in humans. In contrast to the HLA class I genomic structure, the human CD1 duplicons are smaller in size, they lack Alu clocks, and they are interrupted by IGRs at least 4 to 14 times longer than the CD1 genes themselves. The IGRs seem to have been created as "buffer zones" to protect the CD1 genes from disruption by transposable elements.
Publisher: Elsevier BV
Date: 09-1994
DOI: 10.1016/0166-0934(94)90044-2
Abstract: The presence of human cytomegalovirus (CMV) DNA and cellular DNA in leukocytes was detected by duplex polymerase chain reaction (PCR) and quantitated by end-point titration. Two different duplex PCR methods were used to co- lify CMV DNA and a 536 bp fragment of globin DNA. MIE-globin PCR lified a 435 bp fragment of the major immediate early (MIE) gene of CMV DNA whereas the LA-globin PCR lified a 200 bp fragment of the late antigen (LA) gene of CMV DNA. PCR products were separated by electrophoresis in 3% agarose gels and detected by ethidium bromide staining. Amplification of globin DNA was included in the PCR as a positive control to monitor the accuracy and reproducibility of the PCR assay and to provide a reference point for CMV DNA levels. End-point titration PCR using known amounts of recombinant CMV DNA and human placental DNA showed that the end-point titres of the lified CMV DNA correlated directly with the amount of CMV DNA in the s le. The limit of detection of MIE-globin and LA-globin PCR was 1 ng for placental DNA, and 10 fg (1000 copies) for CMV-MIE DNA and 1 fg (100 copies) for CMV-LA DNA, respectively. The amount of CMV DNA was quantitated in leukocytic lysates of 16 immunocompromised patients, who were tested for the presence of CMV in blood by cell culture, and of four normal controls. The blood concentration of CMV DNA, calculated as the number of copies of CMV DNA per microgram of leukocyte DNA, varied between 10(4) and 10(7) in the seven bloods that were CMV-cell-culture-positive, and between 10(2) and 10(4) in the blood of five patients that were CMV-cell-culture-negative. CMV DNA was undetected by PCR in the blood of another eight CMV-negative cases. This study shows that end-point titration and duplex PCR can be used as a simple and rapid method to quantitate CMV DNA in blood of patients that are either CMV-positive or CMV-negative by cell culture. Quantitation of CMV DNA in blood by end-point titration PCR has potential to differentiate between asymptomatic CMV infection and symptomatic CMV disease, and to monitor viral load during viral therapy.
Publisher: Wiley
Date: 04-04-2012
DOI: 10.1111/J.1399-0039.2012.01872.X
Abstract: Although the HLA region contributes to one-third of the genetic factors affecting rheumatoid arthritis (RA), there are few reports on the association of the disease with any of the HLA loci other than the DRB1. In this study we examined the association between RA and the alleles of the six classical HLA loci including DRB1. Six HLA loci (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) of 1659 Japanese subjects (622 cases 488 anti-cyclic citrullinated peptides (CCP) antibody (Ab) positive (82.6%) 103 anti-CCP Ab negative (17.4%) 31 not known and 1037 controls) were genotyped. Disease types and positivity/negativity for CCP autoantibodies were used to stratify the cases. Statistical and genetic assessments were performed by Fisher's exact tests, odds ratio, trend tests and haplotype estimation. None of the HLA loci were significantly associated with CCP sero-negative cases after Bonferroni correction and we therefore limited further analyses to using only the anti CCP-positive RA cases and both anti-CCP positive and anti-CCP negative controls. Some alleles of the non-DRB1 HLA loci showed significant association with RA, which could be explained by linkage disequilibrium with DRB1 alleles. However, DPB1*02:01, DPB1*04:01 and DPB1*09:01 conferred RA risk rotection independently from DRB1. DPB1*02:01 was significantly associated with the highly erosive disease type. The odds ratio of the four HLA-loci haplotypes with DRB1*04:05 and DQB1*04:01, which were the high-risk HLA alleles in Japanese, varied from 1.01 to 5.58. C*07:04, and B*15:18 showed similar P-values and odds ratios to DRB1*04:01, which was located on the same haplotype. This haplotype analysis showed that the DRB1 gene as well as five other HLA loci is required for a more comprehensive understanding of the genetic association between HLA and RA than analyzing DRB1 alone.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2013
DOI: 10.1007/S00251-013-0703-Z
Abstract: Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease involving hair loss, but its pathogenesis remains poorly understood. Many autoimmune diseases are genetically associated with alleles of the human leukocyte antigen (HLA) genes within the major histocompatibility complex. Associations between AA and HLA genes were previously observed in some different ethnic groups. However, the results were inconsistent, and a primary susceptibility HLA gene and/or region has not yet been assigned for AA. The aim of this study was to evaluate whether an allele of the HLA-C locus, HLA-C*07:04, which was strongly associated with AA in Chinese Hans, could be replicated in the Japanese population. The HLA-C locus was genotyped by the SSO method using 156 AA patients and 560 healthy controls. As a consequence, among the 17 alleles detected, only two alleles, C*04:01 (OR = 2.25, CI 95 % = 1.35-3.75, P = 1.84E-03) and C*15:02 (OR = 2.52, CI 95 % = 1.37-4.64, P = 2.90E-03), were significantly associated with AA after Bonferroni correction. Further, the stratification analysis suggested that C*04:01, C*07:02, and C*15:02 represented different AA genetic risk factors in each sub-phenotype.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
DOI: 10.1161/01.HYP.0000257256.77680.02
Abstract: During the past decade, considerable efforts and resources have been devoted to elucidating the multiple genetic and environmental determinants responsible for hypertension and its associated cardiovascular diseases. The success of positional cloning, fine mapping, and linkage analysis based on whole-genome screening, however, has been limited in identifying multiple genetic determinants affecting diseases, suggesting that new research strategies for genome-wide typing may be helpful. Disease association (case–control) studies using microsatellite markers, distributed every 150 kb across the human genome, may have some advantages over linkage, candidate, and single nucleotide polymorphism typing methods in terms of statistical power and linkage disequilibrium for finding genomic regions harboring candidate disease genes, although it is not proven. We have carried out genome-wide mapping using 18 977 microsatellite markers in a Japanese population composed of 385 hypertensive patients and 385 normotensive control subjects. Pooled s le analysis was conducted in a 3-stage genomic screen of 3 independent case–control populations, and 54 markers were extracted from the original 18 977 microsatellite markers. As a final step, each single positive marker was confirmed by in idual typing, and only 19 markers passed this test. We identified 19 allelic loci that were significantly different between the cases of essential hypertension and the controls.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2013
DOI: 10.1038/JHG.2013.2
Abstract: The butyrophilin-like protein 2 gene (BTNL2) within the class III region of the major histocompatibility complex genomic region was identified as a rheumatoid arthritis (RA) susceptibility gene by exome sequencing (19 RA cases) with stepwise filtering analysis, and then validated by Sanger sequencing and association analysis using 432 cases and 432 controls. Logistic regression of the Sanger-sequenced single-nucleotide variants in an association study of 432 cases and 432 controls showed that 12 non-synonymous single-nucleotide polymorphisms (SNPs) in BTNL2 were significantly associated with RA. The lowest P-values were obtained from three SNPs, rs41521946, rs28362677 and rs28362678, which were in absolute linkage disequilibrium: P=4.55E-09, odds ratio=1.88, 95% confidence interval=1.52-2.33. The BTNL2 locates on chromosome 6 between HLA-DRB1 and NOTCH4, and is 170 kb apart from these two genes. Although DRB1 and NOTCH4 were reported to be RA-susceptible, the three BTNL2 SNPs retained significant association with RA when evaluated by the logistic regression with the adjustment for RA-susceptible HLA-DRB1 alleles in Japanese or rs2071282-T in NOTCH4: P=0.0156 and P=0.00368, respectively. These results suggest that the three non-synonymous SNPs in BTNL2 confer RA risk independently from HLA-DRB1 and NOTCH4.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2005
DOI: 10.1007/S00251-004-0745-3
Abstract: There are five polymorphic Alu insertion (POALIN) loci within the major histocompatibility complex (MHC) class I region that have been strongly associated with HLA class I alleles, such as HLA-A1, HLA-A2 and HLA-B57. In order to assess the variability and frequency of POALIN distribution within two common HLA-B haplotypes, we detected the presence of the MHC class I POALIN by PCR in a panel of 15 in iduals with HLA-B57 and 47 homozygous in iduals with 7.1 AH (HLA-B7, -Cw7, -A3) obtained from the Australian Bone Marrow Donor Registry, and also from four families (25 in iduals) containing the HLA-B57 allele. Only two of the 47 HLA-B7 genotypes had a detectable POALIN, whereas all of the HLA-B57 genotypes had at least one or more POALINs present, confirming that certain MHC class I haplotypes are relatively POALIN-free and others are POALIN-enriched. Six distinct HLA-B57 haplotypes, based on differences at the HLA-A locus and three of five POALIN loci, were identified that appear to have evolved by different mechanisms, including either by shuffling different combinations of conserved alpha and beta blocks or by recombination events involving two or more previously generated HLA-B57 haplotypes.
Publisher: Wiley
Date: 13-08-2014
DOI: 10.1111/AGE.12199
Abstract: Microminipigs are extremely small-sized, novel miniature pigs that were recently developed for medical research. The inbred Microminipigs with defined swine leukocyte antigen (SLA) haplotypes are expected to be useful for allo- and xenotransplantation studies and also for association analyses between SLA haplotypes and immunological traits. To establish SLA-defined Microminipig lines, we characterized the polymorphic SLA alleles for three class I (SLA-1, SLA-2 and SLA-3) and two class II (SLA-DRB1 and SLA-DQB1) genes of 14 parental Microminipigs using a high-resolution nucleotide sequence-based typing method. Eleven class I and II haplotypes, including three recombinant haplotypes, were found in the offspring of the parental Microminipigs. Two class I and class II haplotypes, Hp-31.0 (SLA-1*1502-SLA-3*070102-SLA-2*1601) and Hp-0.37 (SLA-DRB1*0701-SLA-DQB1*0502), are novel and have not so far been reported in other pig breeds. Crossover regions were defined by the analysis of 22 microsatellite markers within the SLA class III region of three recombinant haplotypes. The SLA allele and haplotype information of Microminipigs in this study will be useful to establish SLA homozygous lines including three recombinants for transplantation and immunological studies.
Publisher: Frontiers Media SA
Date: 21-07-2022
DOI: 10.3389/FIMMU.2022.938206
Abstract: Acute graft-versus-host disease (aGVHD) is defined as a syndrome of an immunological response of graft to the host that occurs early after allogeneic hematopoietic stem cell transplantation (HCT). This disease is frequently observed even in HCT matched for human leukocyte antigen (HLA) alleles at multiple gene loci. Although the HLA region represents complex and erse genomic characteristics, detailed association analysis is required for the identification of uncharacterized variants that are strongly associated with aGVHD. We genotyped three loci, OR2H2 , HLA-F-AS1 , and HLA-G , that are located in the 460 kb of HLA telomeric region and statistically analyzed the genotypes including HLA-DPB1 with clinical and transplantation outcomes using 338 unrelated bone marrow transplantation (UR-BMT) patient–donor pairs who were matched for HLA-A , HLA-B , HLA-C , HLA-DRB1 , and HLA-DQB1 (HLA-10/10). Multivariate analyses demonstrated that HLA-F-AS1 and HLA-DPB1 mismatches were associated with grade II–IV aGVHD (hazard ratio (HR), 1.76 95% CI, 1.07–2.88 p = 0.026 and HR, 1.59 CI, 1.02–2.49 p = 0.042, respectively). There was no confounding between HLA-F-AS1 and HLA-DPB1 (p = 0.512), suggesting that the HLA-F-AS1 mismatch has a strong effect on aGVHD independently of HLA-DPB1 . Moreover, a stratified analysis suggested possible associations of HLA-F-AS1 , HLA-DPB1 , and/or HLA-G mismatches with grade II–IV aGVHD and the more severe grade III–IV aGVHD. These findings provide new insights into understanding the molecular mechanism of aGVHD caused by HLA-matched UR-BMT.
Publisher: The American Association of Immunologists
Date: 09-2008
DOI: 10.4049/JIMMUNOL.181.5.3393
Abstract: The Mhc is a highly conserved gene region especially interesting to geneticists because of the rapid evolution of gene families found within it. High levels of Mhc genetic ersity often exist within populations. The chicken Mhc is the focus of considerable interest because of the strong, reproducible infectious disease associations found with particular Mhc-B haplotypes. Sequence data for Mhc-B haplotypes have been lacking thereby h ering efforts to systematically resolve which genes within the Mhc-B region contribute to well-defined Mhc-B-associated disease responses. To better understand the genetic factors that generate and maintain genomic ersity in the Mhc-B region, we determined the complete genomic sequence for 14 Mhc-B haplotypes across a region of 59 kb that encompasses 14 gene loci ranging from BG1 to BF2. We compared the sequences using alignment, phylogenetic, and genome profiling methods. We identified gene structural changes, synonymous and non-synonymous polymorphisms, insertions and deletions, and allelic gene rearrangements or exchanges that contribute to haplotype ersity. Mhc-B haplotype ersity appears to be generated by a number of mutational events. We found evidence that some Mhc-B haplotypes are derived by whole- and partial-allelic gene conversion and homologous reciprocal recombination, in addition to nucleotide mutations. These data provide a framework for further analyses of disease associations found among these 14 haplotypes and additional haplotypes segregating and evolving in wild and domesticated populations of chickens.
Publisher: Springer Science and Business Media LLC
Date: 08-2002
DOI: 10.1007/S00251-002-0470-8
Abstract: Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping. However, no genes have been recognized in this candidate region to date. In order to identify a novel candidate gene for DPB from this segment, the expressed sequence tag databases were searched using the genomic sequence. As a result, a cDNA clone was isolated from a human lung cDNA library. This gene, designated C6orf37 (Chromosome 6 open reading frame 37), spans approximately 2.5 kb and consists of two exons encoding a 235-amino acid protein, sharing homology with the mucin-like domain of human zonadhesin, which is a sperm multiple-domain transmembrane protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR analysis detected transcripts from the anti-sense DNA strand of this C6orf37 locus. The gene designated as C6orf37OS (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf37OS were observed in numerous tissues, with most-abundant expression in lung, kidney, and testis. Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf37OS are excellent candidate genes for DPB.
Publisher: Springer Science and Business Media LLC
Date: 12-2002
DOI: 10.1007/S00239-002-2367-4
Abstract: At least two polymorphic Alu insertions have been previously identified and characterized within the class I region of the major histocompatibility complex (MHC). We have identified another two new polymorphic Alu insertions, AluyHJ and AluyHF, located near HLA-J and HLA-F, respectively, within the a block of the MHC. Here we report on (1). the haplotypic relationships between the Alu dimorphisms and the HLA-A locus within a panel of 51 IHW homozygous cell lines representing at least 36 HLA class I haplotypes, (2). the Alu genotype, allele, and haplotype frequencies present in the Australian Caucasians and Japanese populations, and (3). the frequency of association between the different Alu dimorphisms and the HLA-A alleles in 109 Australian Caucasians and 99 Japanese. PCR was used to detect the presence or absence of insertion for AluyHJ, AluyHG, and AluyHF within the DNA s les prepared from the cell lines and the two population groups that had been previously typed for HLA-A. In the homozygous cell lines, all three Alu insertions were found in only one HLA class I haplotype (HLA-A1, -B57, -Cw6), no Alu insertions were detected in six HLA class I haplotypes and one or more of the Alu insertions were found in 29 HLA class I haplotypes. At least one of the Alu insertions was found in about 86% of the Japanese and Australian in iduals, with the AluyHJ generally related inversely to AluyHG and/or AluyHF. The gene frequency of the AluyHJ and AluyHF insertions was significantly different (p 0.05) between the frequencies of AluyHG in the two populations. The Alu haplotype frequencies were also significantly different between the Japanese and the Australians. In the cell lines and the population groups, the AluyHJ insertion was most frequently found associated with HLA-A1 or A24, AluyHG with HLA-A2, and AluyHF with HLA-A2, -A10, or -A26. This study suggests that the three polymorphic Alu elements have been inserted into the a block of the MHC in different progenitor groups and therefore will be useful lineage and linkage markers in human population studies and for elucidating the evolution of HLA class I haplotypes.
Publisher: Elsevier BV
Date: 12-2004
DOI: 10.1016/J.GENE.2004.09.004
Abstract: We describe the isolation and characterization of a full-length cDNA encoded by a gene that was significantly down-regulated in the affected skin of patients with psoriasis vulgaris. The cDNA was isolated from a keratinocyte cDNA library and its sequence was found to correspond to a hypothetical locus recorded in GenBank with the accession number . The nucleotide sequence of the full-length cDNA was found to have an open reading frame of 1365 amino acids and to span approximately 12 kb of genomic DNA with 39 exons on chromosome 16q22. The deduced amino acid sequence contains four distinct structural regions, an RGD motif, a leucine-rich repeat (LRR) region, a tropomodulin domain, and a proline-rich domain. The gene was consequently designated as RLTPR (RGD, leucine-rich repeat, tropomodulin and proline-rich containing protein). The RLTPR hypothetical protein has a functional domain organization similar to Acan125, a myosin-binding protein expressed by Acanthamoeba castellanni. RT-PCR with RLTPR PCR primers lified products from cDNAs prepared from all of the 30 different tissues that we examined including thymus, spleen, colon, skin, skin keratinocytes, skin fibroblasts and fetal skin. During the course of screening the human keratinocyte cDNA library, some alternative splicing was also detected in three regions of the RLTPR gene. In addition, sequence analysis of the RLTPR genes from eight psoriasis patients and eight healthy controls revealed a number of synonymous and nonsynonymous SNPs that may be useful markers for future disease association studies.
Publisher: Frontiers Media SA
Date: 04-10-2018
Publisher: Wiley
Date: 07-2002
DOI: 10.1034/J.1399-0039.2002.600110.X
Abstract: In order to examine the relationship between corneodesmosin (CDSN) and psoriasis we have determined the presence of CDSN polymorphisms by DNA sequencing in (a) nine B-LCL cell lines of major histocompatibility complex ancestral haplotypes known to be associated with psoriasis vulgaris including 13.1AH, 46.1AH, 46.2 and 57.1AH, and in (b) a group of 267 unrelated in iduals comprising Japanese psoriasis patients (n = 101) and Japanese subjects without the disease (n = 166). Three novel CDSN gene sequences were identified. In addition, we have classified the 18 alleles into seven main groups based on phylogeny of non-synonymous substitutions. However, we have found no statistically significant differences between the patients and the unaffected in iduals in any of these groups. These findings indicate that CDSN is not a major psoriasis susceptibility gene.
Publisher: Springer Science and Business Media LLC
Date: 07-04-1999
Abstract: P5 is believed to be a multicopy gene family with at least eight members restricted to the major histocompatibility complex (MHC). Although the function of P5 genes is not known, one of the family members, P5-1, was found previously to be specifically transcribed in lymphoid cells and tissue. In this study, we used computer programs Censor and RepeatMasker, and dot plot analysis to show that the major P5 family members are related in sequence to human endogenous retroviruses, HERV-L and HERV-16. The P5-HERV sequences have at least 60% sequence identity with HERV-L within the pol region but differ significantly within the gag and LTR regions. The LTRs flanking the P5-HERV sequences share about 70% identity with the repeat element LTR16B. Structural analysis of open reading frames (ORFs) confirmed that the P5-1 cDNA is characterized by many stop codons and short putative coding regions resembling the patterns found in the HERV-L nucleotide sequence rather than those found in an mRNA sequence such as expressed by HLA class I genes. A 159 base pair (bp) ORF at the 5' end of the 2535 bp P5-1 mRNA may code for a peptide of 52 amino acids with a domain identical in sequence to the signal peptide of HLA molecules. Furthermore, the P5-1 mRNA is complementary in sequence to retroviral pol mRNA. Therefore, the P5-1 genomic sequence appears to be an ex le of an HERV within the MHC that expresses an antisense transcript with a possible role in immunity to retrovirus infection.
Publisher: Wiley
Date: 05-12-2014
DOI: 10.1111/IJI.12102
Abstract: We investigated the genetic structure and population frequency of an Alu repeat dimorphism (absence or presence) located near the OR12D2 gene within the olfactory receptor gene region telomeric of the alpha HLA class I region (HLA-J, -A, -G, -F). The structurally polymorphic Alu insertion (POALIN) locus rs33972478 that we designated as AluOR and its allele and haplotype frequencies and association with HLA-A and six other structurally polymorphic retroelements (3 Alu, 2 SVA and an HERVK9) were determined in 100 Japanese, 174 Caucasians and 100 African American DNA s les. The AluOR insertion varied in population frequency between 14.4% and 31.5% with significant differences between the Japanese and Caucasians, but not between the Caucasian and African Americans. Although AluOR is located 600 kb from the HLA-A gene, there was a significant linkage disequilibrium between the two loci and a high percentage association of the AluOR insertion with HLA-A29 (79%) in Caucasians and HLA-A31 (69.4%) in Japanese. Inferred haplotypes among three-locus to eight-locus haplotype structures showed maximum differences between the populations with the eight-locus haplotypes. The most frequent multilocus haplotype shared between the populations was the HLA-A2 allele in combination with the AluHG insertion. The AluOR whether investigated alone or together with the HLA class I alleles and other dimorphic retroelements is an informative ancestral marker for the identification of lineages and variations within the same and/or different populations and for examining the linkage and crossing-over between the HLA and OR genomic regions in the extended MHC.
Publisher: Wiley
Date: 12-1988
Abstract: Filter in situ hybridisation (FISH) was used to detect the presence of DNA of human papillomavirus (HPV) types 6/11 or 16/18 in cell scrapes (CYTOFISH) and formalin-fixed, paraffin-embedded biopsies (HISTOFISH) taken from the uterine cervices of 19 women. Paraffin tissue sections collected for HISTOFISH were either digested with pepsin or lysed with alkali/Triton X-100. The digest or lysate of the tissue sections and cell scrapes were applied to nylon or nitrocellulose membranes for nucleic acid hybridisation using 32P-labeled HPV-DNA probes. CYTOFISH and HISTOFISH were compared directly by taking s les for each method from the cervices of the same women. Of 19 women examined by colposcopy, cytology, and histology, eight were assessed as normal and 11 had evidence of a cervical disorder and/or the presence of HPV infection. Whereas no HPV-DNA was detected in the normal cases, the presence of HPV-DNAs was detected by both CYTOFISH and HISTOFISH in 11 cases with histological evidence of HPV infection and/or dysplasia. In these HPV positive cases, eight contained HPV 16/18, two HPV 6/11, and one a mixed infection of HPV 6/11/16/18. The high correlation between the results of CYTOFISH and HISTOFISH shows that formalin-fixed, paraffin-embedded cervical biopsies are suitable specimens for the detection and typing of HPV-DNA by FISH. Both CYTOFISH and HISTOFISH should facilitate studies on the prevalence and distribution of HPVs and their association with neoplasia.
Publisher: Springer Science and Business Media LLC
Date: 04-2003
DOI: 10.1007/S00239-002-2410-5
Abstract: The human S100 gene family encodes the EF-hand superfamily of calcium-binding proteins, with at least 14 family members clustered relatively closely together on chromosome 1q21. We have analyzed the most recently available genomic sequence of the human S100 gene cluster for evidence of tandem gene duplications during primate evolutionary history. The sequences obtained from both GenBank and GoldenPath were analyzed in detail using various comparative sequence analysis tools. We found that of the S100A genes clustered relatively closely together within a genomic region of 260 kb, only the S100A7 (psoriasin) gene region showed evidence of recent duplications. The S100A7 gene duplicated region is composed of three distinct genomic regions, 33, 11, and 31 kb, respectively, that together harbor at least five identifiable S100A7-like genes. Regions 1 and 3 are in opposite orientation to each other, but each region carries two S100A7-like genes separated by an 11-kb intergenic region (region 2) that has only one S100A7-like gene, providing limited sequence resemblance to regions 1 and 3. The duplicated genomic regions 1 and 3 share a number of different retroelements including five Alu subfamily members that serve as molecular clocks. The shared (paralogous) Alu S insertions suggest that regions 1 and 3 were probably duplicated during or after the phase of AluS lification some 30-40 mya. We used PCR to lify an indel within intron 1 of the S100A7a and S100A7c genes that gave the same two expected product sizes using 40 human DNA s les and 1 chimpanzee s le, therefore confirming the presence of the region 1 and 3 duplication in these species. Comparative genomic analysis of the other S100 gene members shows no similarity between intergenic regions, suggesting that they erged long before the emergence of the primates. This view was supported by the phylogenetic analysis of different human S100 proteins including the human S100A7 protein members. The S100A7 protein, also known as psoriasin, has important functions as a mediator and regulator in skin differentiation and disease (psoriasis), in breast cancer, and as a chemotactic factor for inflammatory cells. This is the first report of five copies of the S100A7 gene in the human genome, which may impact on our understanding of the possible dose effects of these genes in inflammation and normal skin development and pathogenesis.
Publisher: Cold Spring Harbor Laboratory
Date: 10-2000
DOI: 10.1101/GR.127200
Abstract: The human major histocompatibility complex (MHC) is characterized by polymorphic multicopy gene families, such as HLA and MIC (PERB11) duplications insertions and deletions (indels) and uneven rates of recombination. Polymorphisms at the antigen recognition sites of the HLA class I and II genes and at associated neutral sites have been attributed to balancing selection and a hitchhiking effect, respectively. We, and others, have previously shown that nucleotide ersity between MHC haplotypes at non-HLA sites is unusually high ( %) and up to several times greater than elsewhere in the genome (0.08%–0.2%). We report here the most extensive analysis of nucleotide ersity within a continuous sequence in the genome. We constructed a single nucleotide polymorphism (SNP) profile that reveals a pattern of extreme but interrupted levels of nucleotide ersity by comparing a continuous sequence within haplotypes in three genomic subregions of the MHC. A comparison of several haplotypes within one of the genomic subregions containing the HLA-B and -C loci suggests that positive selection is operating over the whole subgenomic region, including HLA and non-HLA genes. [The sequence data for the multiple haplotype comparisons within the class I region have been submitted to DDBJ/EMBL/GenBank under accession nos. AF029061 , AF029062 , and AB031005 – AB031010 . Additional sequence data have been submitted to the DDBJ data library under accession nos. AB031005 –AB03101 and AF029061 – AF029062 .]
Publisher: Springer Science and Business Media LLC
Date: 11-11-2005
DOI: 10.1007/S00109-005-0721-X
Abstract: Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. HUG95A Affymetrix DNA chips that contained oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student t-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signalling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases, including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T cells. Some of the up-regulated genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the up-regulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic interferon- and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.
Publisher: Wiley
Date: 12-1989
DOI: 10.1038/ICB.1989.59
Abstract: The presence of papillomaviral-like DNA has been described in ultraviolet light-induced tumours in the skin of the hairless mouse (14). Here we describe the effects of the inoculation of cell-free extracts of ultraviolet light-induced tumours into the scarified skin of normal hairless mice, prior to exposure of the mice to a cumulative carcinogenic dose of ultraviolet light. Extracts from papillomas or squamous cell carcinomas enhanced the susceptibility of the inoculated mice to ultraviolet light-induced tumorigenesis, if the extracts contained papillomaviral DNA sequences detected by cross-hybridization with Mastomys natalensis papillomaviral DNA. The recipient mice developed a greater tumour incidence, tumour yield, tumour diameter and degree of malignancy.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2005
DOI: 10.1007/S00251-005-0048-3
Abstract: We have developed a new high-throughput, high-resolution genotyping method for the detection of alleles at the human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 loci by combining polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (SSOPs) protocols with the Luminex 100 xMAP flow cytometry dual-laser system to quantitate fluorescently labeled oligonucleotides attached to color-coded microbeads. In order to detect the HLA alleles with a frequency of more than 0.1% in the Japanese population, we created 48 oligonucleotide probes for the HLA-A locus, 61 for HLA-B, 34 for HLA-C, and 51 for HLA-DRB1. The accuracy of the PCR-SSOP-Luminex method was determined by comparing it to the nucleotide sequencing method after subcloning into the plasmid vector using 150 multinational control s les obtained from the International HLA DNA Exchange University of California Los Angeles. In addition, we performed the PCR-SSOP-Luminex method for HLA allele typing on DNA s les collected from 1,018 Japanese volunteers. Overall, the genotyping method exhibited an accuracy of 85.91% for HLA-A, 85.03% for HLA-B, 97.32% for HLA-C, and 90.67% for HLA-DRB1 using 150 control s les, and 100% for HLA-A and -C, 99.90% for HLA-B, and 99.95% for HLA-DRB1 in 1,018 Japanese s les. The PCR-SSOP-Luminex method provides a simple, accurate, and rapid approach toward multiplex genotyping of HLA alleles to the four-digit or higher level of resolution in the Japanese population. It takes only approximately 5 h from DNA extraction to the definition of HLA four-digit alleles at the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci for 96 s les when handled by a single typist.
Publisher: Wiley
Date: 05-03-2004
DOI: 10.1111/J.0001-2815.2004.00200.X
Abstract: In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.
Publisher: MDPI AG
Date: 06-03-2023
Abstract: Polymorphisms of canine leukocyte antigen (DLA) class I (DLA-88 and DLA-12/88L) and class II (DLA-DRB1) genes are important for disease susceptibility studies, but information on the genetic ersity among dog breeds is still lacking. To better elucidate the polymorphism and genetic ersity between breeds, we genotyped DLA-88, DLA-12/88L, and DLA-DRB1 loci using 829 dogs of 59 breeds in Japan. Genotyping by Sanger sequencing identified 89, 43, and 61 alleles in DLA-88, DLA-12/88L, and DLA-DRB1 loci, respectively, and a total of 131 DLA-88–DLA-12/88L–DLA-DRB1 haplotypes (88-12/88L-DRB1) were detected more than once. Of the 829 dogs, 198 were homozygotes for one of the 52 different 88-12/88L-DRB1 haplotypes (homozygosity rate: 23.8%). Statistical modeling suggests that 90% of the DLA homozygotes or heterozygotes with one or other of the 52 different 88-12/88L-DRB1 haplotypes within somatic stem cell lines would benefit graft outcome after 88-12/88L-DRB1-matched transplantation. As previously reported for DLA class II haplotypes, the ersity of 88-12/88L-DRB1 haplotypes varied remarkably between breeds but was relatively conserved within most breeds. Therefore, the genetic characteristics of high DLA homozygosity rate and poor DLA ersity within a breed are useful for transplantation therapy, but they may affect biological fitness as homozygosity progresses.
Publisher: Wiley
Date: 11-10-2011
DOI: 10.1111/J.1399-0039.2011.01776.X
Abstract: We investigated structurally polymorphic Alu insertions (POALINs) at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-A, -B, and -C genes in three populations, the Australian Caucasians, Japanese, and African Americans. The POALINs varied in allelic frequency between 0% and 42.3% with significant differences between populations at three of the five loci. The linkage disequilibrium (LD) between Alu insertions and the HLA-A, -B, or -C alleles and previously published polymorphic retroelements (four SVA and human endogenous retrovirus type 9 (HERVK9) loci) within the class I region of the MHC were calculated in pairwise analyses of haplotypes to show strong allelic associations and possible crossing-over events between some loci. Each POALIN was in significant LD with a variety of HLA-A, -B, or -C two-digit alleles probably as a result of hitchhiking. The POALINs helped to further stratify the HLA-A:B:C haplotypes into different POALIN:HLA-A:B:C haplotype frequencies. Of the multilocus haplotype analyses, the seven- and eight-locus haplotypes showed the largest number of differences between the populations, and fewer matched haplotypes between populations that ranged, for ex le, from 49% for HLA-B:HLA-A haplotypes to 7% for AluMICB:HLA-B:HLA-C:AluTF:AluHJ:HLA-A:AluHG:AluTF haplotypes in the Japanese. This comparative study of multilocus POALINs in the HLA class I region of three ethnic populations shows that POALINs alone or together with the HLA class I alleles and other retroelements are informative ancestral markers for assessing the interrelationship of HLA class I haplotype lineages, LD, and genetic ersity within the same and/or different populations.
Publisher: Wiley
Date: 15-12-2010
DOI: 10.1111/J.1399-0039.2009.01391.X
Abstract: Endometriosis is a female disorder characterized by the presence of uterine endometrial tissue in ectopic loci. Previous studies reported a higher prevalence of particular human leukocyte antigen (HLA) in endometriosis. In order to confirm the association between endometriosis and the HLA region, 15 polymorphic microsatellite markers distributed in the HLA class II to class III region were subjected to association analysis by polymerase chain reaction (PCR)-based DNA typing of 89 patients and 136 healthy controls. Statistical analysis of the allelic frequency at each microsatellite locus showed that there were no statistically significant differences in the allele frequency distributions between the cases and controls. This finding suggests that the etiology of endometriosis does not involve the HLA class II genomic region and a portion of class III genomic region in the Japanese population.
Publisher: Springer Science and Business Media LLC
Date: 08-2002
Publisher: Springer Science and Business Media LLC
Date: 18-03-2009
DOI: 10.1007/S00251-009-0364-0
Abstract: The study of the association of the Human Leukocyte Antigen (HLA) alleles and polymorphic retrotransposons such as Alu, HERV, and LTR at various loci within the Major Histocompatibility Complex allows for a better identification and stratification of disease associations and the origins of HLA haplotypes in different populations. This paper provides sequence and association data on two structurally polymorphic MER9-LTR retrotransposons that are located 54 kb apart and in close proximity to the multiallelic HLA-A gene involved in the regulation of the human immune system. Direct DNA sequencing and analysis of the PCR products identified DNA nucleotide variations between the MER9-LTR sequences at the two loci and their associations with HLA-A alleles as potential haplotype and evolutionary markers. All MER9-LTR sequences were haplotypic when associated with common HLA-A alleles. The number of SNP loci was 2.5 times greater for the solo LTR at the AK locus, which is located closer to the HLA-A gene than the solo or 3' LTR at the HG locus. Our study shows that the nucleotide variations of the MER9-LTR DNA sequences are additional informative markers in fine mapping HLA-A genomic haplotypes for future population, evolutionary, and disease studies.
Publisher: Wiley
Date: 05-2004
Publisher: Elsevier BV
Date: 06-2004
Publisher: Public Library of Science (PLoS)
Date: 25-11-2020
DOI: 10.1371/JOURNAL.PONE.0242572
Abstract: Cluster of differentiation 4 (CD4) molecule expressed on the leukocytes is known to function as a co-receptor for class II major histocompatibility complex (MHC) binding to T cell receptor (TCR) on helper T cells. We previously identified two CD4 alleles (CD4.A and CD4.B) in a Microminipig population based on nucleotide sequencing and PCR detection of their gene sequences. However, CD4.B protein expression was not examined because of the unavailability of a reactive antibody to a CD4.B epitope. In this study, we have produced two swine-specific monoclonal antibodies (mAbs) against CD4.B molecules, one that recognizes only CD4.B (b1D7) and the other that recognizes both the CD4.A and CD4.B alleles (x1E10) and that can be used to distinguish CD4 T cell subsets by flow cytometry and immunohistochemistry. Using these two mAbs, we identified CD4.A and CD4.B allele-specific proteins on the surface of CD4.A (+/+) and CD4.B (+/+) T cells at a similar level of expression. Moreover, stimulation of peripheral blood mononuclear cells (PBMCs) derived from CD4.A (+/+) and CD4.B (+/+) swine with toxic shock syndrome toxin-1 (TSST-1) in vitro similarly activated both groups of cells that exhibited a slight increase in the CD4/CD8 double positive (DP) cell ratio. A large portion of the DP cells from the allelic CD4.A (+/+) and CD4.B (+/+) groups enhanced the total CD4 and class I swine leukocyte antigen (SLA) expression. The x1E10 mAb delayed and reduced the TSST-1-induced activation of CD4 T cells. Thus, CD4.B appears to be a functional protein whose expression on activated T cells is analogous to CD4.A.
Publisher: Frontiers Media SA
Date: 28-05-2021
DOI: 10.3389/FGENE.2021.665899
Abstract: The major histocompatibility complex (MHC) on chromosome 6p21 is one of the most single-nucleotide polymorphism (SNP)-dense regions of the human genome and a prime model for the study and understanding of conserved sequence polymorphisms and structural ersity of ancestral haplotypes/conserved extended haplotypes. This study aimed to follow up on a previous analysis of the MHC class I region by using the same set of 95 MHC haplotype sequences downloaded from a publicly available BioProject database at the National Center for Biotechnology Information to identify and characterize the polymorphic human leukocyte antigen (HLA)- class II genes, the MTCO3P1 pseudogene alleles, the indels of transposable elements as haplotypic lineage markers, and SNP-density crossover (XO) loci at haplotype junctions in DNA sequence alignments of different haplotypes across the extended class II region (∼1 Mb) from the telomeric PRRT1 gene in class III to the COL11A2 gene at the centromeric end of class II. We identified 42 haplotypic indels (20 Alu, 7 SVA, 13 LTR or MERs, and 2 indels composed of a mosaic of different transposable elements) linked to particular HLA-class II alleles. Comparative sequence analyses of 136 haplotype pairs revealed 98 unique XO sites between SNP-poor and SNP-rich genomic segments with considerable haplotype shuffling located in the proximity of putative recombination hotspots. The majority of XO sites occurred across various regions including in the vicinity of MTCO3P1 between HLA-DQB1 and HLA-DQB3 , between HLA-DQB2 and HLA-DOB , between DOB and TAP2 , and between HLA-DOA and HLA-DPA1 , where most XOs were within a HERVK22 sequence. We also determined the genomic positions of the PRDM9-recombination suppression sequence motif ATCCATG/CATGGAT and the PRDM9 recombination activation partial binding motif CCTCCCCT/AGGGGAG in the class II region of the human reference genome (NC_ 000006) relative to published meiotic recombination positions. Both the recombination and anti-recombination PRDM9 binding motifs were widely distributed throughout the class II genomic regions with 50% or more found within repeat elements the anti-recombination motifs were found mostly in L1 fragmented repeats. This study shows substantial haplotype shuffling between different polymorphic blocks and confirms the presence of numerous putative ancestral recombination sites across the class II region between various HLA class II genes.
Publisher: Wiley
Date: 12-1981
DOI: 10.1038/ICB.1981.66
Abstract: A study was undertaken to determine by radioimmunoassay the changes in concentrations of cortisol in the mammary secretion of in idual women during late pregnancy, lactogenesis, established lactation and after cessation of breast-feeding. The concentration of cortisol in colostrum averaged 7.5% of that found in serum during late pregnancy. The concentration of cortisol (mean +/- S.E.M.) was relatively high in the mammary secretions during late pregnancy (25.5 +/- 1.8 ng/ml) and decreased within 2 days after delivery (10.2 +/- 2.0 ng/ml) to reach low values by 10 days post partum (1.8 +/- 0.7 ng/ml). During advanced lactation the cortisol values varied between 0.2 to 32 ng/ml but the mean concentration was significantly (p less than 0.05) less (7.2 +/- 0.8 ng/ml, n = 75) than during late pregnancy. With the abrupt termination of breast-feeding, the concentration of cortisol generally increased above the values determined during established lactation, but, even during involution, the progressive changes in concentration varied markedly (range 0.5-40.0 ng/ml). The function of milk cortisol for the newborn is now known. However, it is possible that cortisol in breast milk may help to control the transport of fluids and salts from the gastrointestinal tract of infants.
Publisher: Oxford University Press (OUP)
Date: 07-2004
DOI: 10.1093/NAR/GKH448
Publisher: Springer Science and Business Media LLC
Date: 07-2004
DOI: 10.1007/S00251-004-0690-1
Abstract: Two quail lines, H and L, which were developed for high (H) and low (L) antibody production against inactivated Newcastle disease virus antigen, were used to examine differences in the organization, structure and expression of the quail Mhc class IIB genes. Four Coja class IIB genes in the H line and ten Coja class IIB genes in the L line were identified by gene lification using standard and long-range PCRs and sequencing of the lified products. RFLP analysis, sequencing and gene mapping revealed that the H line was fixed for a single class IIB haplotype, which we have designated CojaII-02HL- CojaII-01HL. In contrast, evidence was found for two class IIB haplotypes segregating in the L line. Some in iduals were found to be homozygous for haplotype CojaII-08L- CojaII-07L and others were found to be heterozygous CojaII-08L- CojaII-07L/ CojaII-02HL- CojaII-01HL. However, expression of CojaII-02HL- CojaII-01HL was not detected in the L line. SRBC immunization induced a measurable antibody response in the serum and a line-specific class IIB gene expression in the peripheral white blood cells. CojaII-01HL was expressed at the highest level in the H line and CojaII-07L in the L line. The expression of the class IIB mRNA reached the highest level at approximately 1 week after the primary antibody response and then declined exponentially. The antibody and class IIB gene expression data obtained in response to SRBC immunization provide further evidence that quails within the L line had reduced immunocompetence compared with those in the H line.
Publisher: Elsevier BV
Date: 1998
DOI: 10.1080/00313029800169705
Abstract: Fifty-nine enterococci isolated from 18 patients in an intensive care unit (ICU) and 21 patients in general wards (GW) at Royal Perth Hospital (RPH) during a period of 14 months were examined for antibiotic resistance by susceptibility testing and DNA polymorphism by pulsed-field gel electrophoresis. The study showed that penicillin-resistant Enterococcus faecium is a common nosocomial isolate in ICU. The DNA patterns of various strains of E. faecium and E. faecalis were closely related in most consecutive isolates from the same patients but were generally different for isolates from different patients. Thirty two different DNA patterns were identified for 59 isolates from 39 patients. Identical or similar DNA patterns were also identified for some isolates from different patients, suggesting that cross-infection had occurred between patients in ICU and GW. These data suggest that cross-infection occurred more commonly in ICU than in GW and are consistent with the known higher risk of ICU patients for nosocomial infection.
Publisher: InTech
Date: 14-01-2016
DOI: 10.5772/61964
Publisher: Public Library of Science (PLoS)
Date: 19-10-2016
Publisher: InTech
Date: 14-01-2016
DOI: 10.5772/61842
Publisher: MDPI AG
Date: 17-10-2019
DOI: 10.3390/CELLS8101270
Abstract: The human Major Histocompatibility Complex (MHC) genes are part of the supra‐locus onchromosome 6p21 known as the human leukocyte antigen (HLA) system [...]
Publisher: Springer Science and Business Media LLC
Date: 27-09-2017
DOI: 10.1007/S00251-017-1031-5
Abstract: The current information on the polymorphism variation and haplotype structure of the domestic dog leukocyte antigen (DLA) genes is limited in comparison to other experimental animals. In this paper, to better elucidate the degree and types of polymorphisms and genetic differences for DLA-88, DLA-12 and DLA-64, we genotyped four families of 38 beagles and another 404 unrelated dogs representing 49 breeds by RT-PCR based Sanger sequencing. We also sequenced and analyzed the genomic organization of the DLA-88 and DLA-12 gene segments to better define these two-gene DLA haplotypes more precisely. We identified 45 alleles for DLA-88, 15 for DLA-12 and six for DLA-64, of which 20, 14 and six, respectively, were newly described alleles. Therefore, this study shows that the DLA-12 and DLA-64 loci are far more polymorphic than previously reported. Phylogenetic analysis strongly supported that the DLA-88, DLA-12 and DLA-64 alleles were independently generated after the original ergence of the DLA-79 alleles. Two distinct DLA-88 and DLA-12 haplotype structures, tentatively named DLA-88-DLA-12 and DLA-88-DLA-88L, were identified, and the novel haplotype DLA-88-DLA-88L contributed to 32.7% of the unrelated dogs. Quantitative real-time PCR analysis showed that the gene expression levels of DLA-88L and DLA-88 were similar, and that the gene expression level of DLA-12 was significantly lower. In addition, haplotype frequency estimations using frequently occurring alleles revealed 45 different DLA-class I haplotypes (88-88L/12-64) overall, and 22 different DLA-class I haplotypes in homozygous dogs for 18 breeds and mongrels.
Publisher: Wiley
Date: 06-1993
DOI: 10.1046/J.1537-2995.1993.33693296813.X
Abstract: A polymerase chain reaction (PCR) assay was developed and optimized to detect cytomegalovirus (CMV) DNA in the blood of 86 normal donors who had originally tested seropositive for CMV. Evidence of previous or current infection with CMV was determined by rescreening of the blood for CMV antibodies and by detecting the presence of infectious virus in the white cells by cell culture. DNA was extracted from the blood of donors by a manual or an automated method and lified by PCR using primers from the major immediate early gene of CMV DNA. The lified product was detected by visualization of a fluorescent 435-base pair DNA band in an electrophoretic agarose gel after ethidium bromide staining and confirmed by slot-blot DNA hybridization using an oligonucleotide probe with complementarity for the major immediate early gene. Seven (8%) of the 86 donors were positive for CMV DNA in both fluorescence and hybridization studies. These donors were also antibody positive. While 74 (86%) of the 86 donors were positive for the presence of CMV antibodies in enzyme-linked immunosorbent assay, none was positive for virus in cell culture. PCR has the potential to be an effective and reliable procedure for the detection of CMV DNA in donor blood, but further study is required for this technique to be used for diagnostic or routine screening purposes.
Publisher: Frontiers Media SA
Date: 15-07-2020
Publisher: Wiley
Date: 09-05-2010
DOI: 10.1111/J.1399-0039.2010.01499.X
Abstract: We investigated polymorphic Alu insertion (POALIN) frequencies at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-B and -Cw genes in seven different Chinese ethnic populations, the Han, Bulang, Wa, Dai, Maonan, Hani and Jinuo. The POALINs varied in frequency between 0% and 42.3% with significant differences between populations at all of the loci. Each POALIN was in significant linkage disequilibrium with a variety of HLA-B or -Cw four-digit alleles. The percentage association between Alu insertions and the HLA-B or -Cw alleles was calculated in pairwise analyses of haplotypes to show possible crossing over events between loci. The POALIN insertions also helped to further stratify the HLA-B:-Cw haplotypes into different POALIN:HLA-B:HLA-Cw haplotype frequencies. Of the two-locus, five-locus and seven-locus haplotype analyses, the seven-locus haplotypes showed the largest number of differences between the populations. The most common multilocus haplotype in Han was MICB*1:B*4601:Cw*0102:TF*1:HJ*1:HG*2:HF*1 (15.6%) associated with the AluHG insertion, whereas the second most common multilocus haplotype in Han was MICB*1:B*1502:Cw*0801:TF*1:HJ*2:HG*1:HF*1 (11.8%) associated with the AluHJ insertion. This comparative study of multilocus POALINs in the HLA class I region of seven Chinese ethnic populations shows that POALINs alone or together with the HLA class I alleles are informative genetic markers for the identification of HLA class I allele and haplotype lineages and variations such as crossing over events within the same and/or different populations.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2006
DOI: 10.1007/S00251-006-0155-9
Abstract: A previous study in China first indicated that the transforming growth factor-induced factor (TGIF) is a probable candidate gene for high myopia. The purpose of our study was to investigate whether there are significant associations between high myopia and single nucleotide polymorphism (SNP) variants in the TGIF gene of Japanese subjects. Genomic DNA was collected from 330 Japanese subjects with high myopia and at a level refractive error was less than -9.25 Dsph and 330 randomized controls without high myopia. Thirteen SNPs were detected by polymerase chain reaction (PCR) and primer extension or by PCR and SNP-specific fluorogenic probes in all of the cases and controls. Thirteen SNPs were found within the TGIF genes of the cases and controls. Two of the SNPs were monomorphic and none of the 13 SNPs showed a significant result. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index of >0.8 for D' and >0.4 for r(2). We found no statistical association between any of the 13 SNPs located on the TGIF gene and high myopia in Japanese subjects. Based on our study using Japanese subjects and the previous studies of TGIF gene polymorphism in Chinese and northern European subjects with myopia, there is no convincing evidence to prove a connection between nucleotide sequence variations in TGIF and high myopia.
Publisher: Wiley
Date: 28-09-2012
DOI: 10.1111/TAN.12007
Abstract: Distinct human leukocyte antigen (HLA) allele and haplotype distributions occur in the northern and southern Han populations of China. However, different ethnic groups in China show limited regional distributions for many HLA alleles and haplotypes. Therefore, it is necessary and meaningful to study the differences in HLA allele and haplotype distribution for northern and southern ethnic groups of China. A total of 428 unrelated in iduals from the Lisu, Nu, Tu and Yugur ethnic populations were genotyped for HLA-A, -B, -C and -DRB1 alleles using the PCR-Luminex typing method. The frequencies of HLA alleles and statistically inferred haplotypes were calculated. A total of 29 HLA-A, 54 HLA-B, 27 HLA-C and 41 HLA-DRB1 alleles were spread throughout these four populations with distinct allele and deduced haplotype frequencies between populations. Some alleles and deduced haplotypes exhibited significantly different distributions between northern (Tu and Yugur) and southern groups (Lisu and Nu). A phylogenetic tree and principal component analysis were used to compare the HLA polymorphism between our dataset and 19 other eastern and southeastern Asian populations. This analysis showed that Lisu and Nu belong to a cluster of southern ethnic groups, while Tu and Yugur are most closely related to other northern groups. Thus, distinct ethnic population histories were revealed by analyzing HLA allelic polymorphisms with the HLA profiles of the Lisu and Nu southern Chinese ethnic groups clearly different from the Tu and Yugur northern ethnic groups. The results will be useful for future association studies of infectious disease and contribute toward a more efficient search of organ/tissue matches for transplantation.
Publisher: Springer Science and Business Media LLC
Date: 08-2001
Abstract: The AluYb8 sequences are a subfamily of short interspersed Alu retroelements that have been lified within the human genome during recent evolutionary time and are useful polymorphic markers for studies on the origin of human populations. We have identified a new member of the Yb8 subfamily, AluyHG, located between the HLA-H and -G genes and 88-kb telomeric of the highly polymorphic HLA-A gene within the alpha block of the major histocompatibility complex (MHC). The AluyHG element was characterised with a view to examining the association between AluyHG and HLA-A polymorphism and reconstructing the history of the MHC alpha block. A specific primer pair was designed for a simple PCR assay to detect the absence or presence (dimorphism) of the AluyHG element within the DNA s les prepared from a panel of 46 homozygous cell-lines containing complete or recombinant ancestral haplotypes (AH) of erse ethnic origin and 92 Caucasoid and Asian subjects on which HLA-A typing was available. The AluyHG insertion was most strongly associated with HLA-A2 and, to a lesser degree with HLA-A1, -A3, -A11, and A-19. The gene frequency of the AluyHG insertion for 146 Caucasians and 94 Chinese-Han was 0.30 and 0.32 and there was no significant difference between the observed and expected frequencies. The results of the association studies and the phylogenetic analysis of HLA-A alleles suggest that the AluyHG sequence was integrated within the progenitor of HLA-A2, but has been transferred by recombination to other human ancestral populations. In this regard, the dimorphic AluyHG element is an important diagnostic marker for HLA association studies and could help in elucidating the evolution and functions of the MHC alpha block and polymorphism within and between ancestral haplotypes.
Publisher: Springer Science and Business Media LLC
Date: 07-1999
DOI: 10.1007/PL00006537
Abstract: The recent availability of genomic sequence information for the class I region of the MHC has provided an opportunity to examine the genomic organization of HLA class I (HLAcI) and PERB11/MIC genes with a view to explaining their evolution from the perspective of extended genomic duplications rather than by simple gene duplications and/or gene conversion events. Analysis of genomic sequence from two regions of the MHC (the alpha- and beta-blocks) revealed that at least 6 PERB11 and 14 HLAcI genes, pseudogenes, and gene fragments are contained within extended duplicated segments. Each segment was searched for the presence of shared (paralogous) retroelements by RepeatMasker in order to use them as markers of evolution, genetic rearrangements, and evidence of segmental duplications. Shared Alu elements and other retroelements allowed the duplicated segments to be classified into five distinct groups (A to E) that could be further distilled down to an ancient preduplication segment containing a HLA and PERB11 gene, an endogenous retrovirus (HERV-16), and distinctive retroelements. The breakpoints within and between the different HLAcI segments were found mainly within the PERB11 and HLA genes, HERV-16, and other retroelements, suggesting that the latter have played a major role in duplication and indel events leading to the present organization of PERB11 and HLAcI genes. On the basis of the features contained within the segments, a coevolutionary model premised on tandem duplication of single and multipartite genomic segments is proposed. The model is used to explain the origins and genomic organization of retroelements, HERV-16, DNA transposons, PERB11, and HLAcI genes as distinct segmental combinations within the alpha- and beta-blocks of the human MHC.
Publisher: Elsevier BV
Date: 05-1995
DOI: 10.1016/0166-0934(95)00004-E
Abstract: Major capsid proteins (MCPs) of various papillomaviruses have recently been expressed in heterologous cells as soluble and functional polypeptides. The host cells for producing these proteins have so far been of eukaryotic origin however, E. coli has potential utility a host, with advantages over eukaryotic cells such as relatively simple culture requirements and greater ease of mutation of expressed sequences. We studied the expression by E. coli of the MCP of human papillomavirus type 16 (HPV16) using the gene derived from the 'prototype' HPV16 genome. Using expression vector pTrc99A, the protein was produced in full-length unfused form at levels of 3-4% of cell protein. Soluble polypeptide was detected, albeit at low levels. The level of solubility was not increased by growing cells at low temperature and slowing the rate of protein synthesis. The soluble protein was degraded at its carboxy terminus by an outer membrane protease of E. coli, OmpT, giving rise to two slightly shortened protein species of 52K and 56K in addition to the full-length 57K polypeptide. Since the MCP of prototype HPV16 is known to be prone to excessive aggregation compared with other papillomaviral MCPs, the recovery of soluble polypeptide indicates that E. coli is worth consideration as an alternative host to eukaryotes for producing these proteins.
Publisher: Elsevier BV
Date: 09-1999
DOI: 10.1016/S0378-1119(99)00255-3
Abstract: The recent availability of the genomic sequence spanning the central and telomeric end of the major histocompatibility complex (MHC) has allowed a detailed study of its organisation, gene content and level of nucleotide variability. Previous analyses of nucleotide variability in the MHC have focused on the coding regions of the human leukocyte antigen (HLA) Class I and II genes. Non-coding nucleotide variability has been considered a by-product of exonic ersity. However, with the advent of genomic sequencing, the extent of non-coding nucleotide variability within the MHC has just begun to be appreciated. In this study, we compared different human haplotypes in 370 kb of sequence in the central region of the MHC to show the following: 1. unusually high levels of non-coding nucleotide variability, up to 80 times greater than elsewhere in the genome 2. non-coding nucleotide variability greater than 1% at nucleotide sites distant to the Class I genes 3. nucleotide variability greater than 1% maintained over regions containing highly linked loci and 4. distinct troughs and peaks in the level of nucleotide variability. We will discuss these observations in relation to a possible role of nucleotide variability in the organisation of the MHC.
Publisher: Springer Science and Business Media LLC
Date: 05-04-2012
DOI: 10.1038/HR.2012.41
Abstract: The Millennium Genome Project for Hypertension was started in 2000 to identify genetic variants conferring susceptibility to hypertension, with the aim of furthering the understanding of the pathogenesis of this condition and realizing genome-based personalized medical care. Two different approaches were launched, genome-wide association analysis using single-nucleotide polymorphisms (SNPs) and microsatellite markers, and systematic candidate gene analysis, under the hypothesis that common variants have an important role in the etiology of common diseases. These multilateral approaches identified ATP2B1 as a gene responsible for hypertension in not only Japanese but also Caucasians. The high blood pressure susceptibility conferred by certain alleles of ATP2B1 has been widely replicated in various populations. Ex vivo mRNA expression analysis in umbilical artery smooth muscle cells indicated that reduced expression of this gene associated with the risk allele may be an underlying mechanism relating the ATP2B1 variant to hypertension. However, the effect size of a SNP was too small to clarify the entire picture of the genetic basis of hypertension. Further, dense genome analysis with accurate phenotype data may be required.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2010
DOI: 10.1007/S10875-010-9426-1
Abstract: Human CD93 has a molecular weight of about 100 kDa and is selectively expressed by myeloid cell lineages in peripheral blood (PB) mononuclear cells. Although CD93 was initially identified as a receptor for complement component 1, subcomponent q phagocytosis (C1qRp) involved in the C1q-mediated enhancement of the phagocytosis of various antigens, several recent studies have reported that CD93 is not a receptor for the C1q-mediated enhancement of phagocytosis. The expression patterns of CD93 have been previously investigated in PB mononuclear cells (lymphocytes, monocytes, and granulocytes) from adult PB and neonatal umbilical cord blood (UCB), and the expression of CD93 was not found on lymphocytes from either normal adult PB or neonatal UCB. However, the detection of CD93 expression in neonatal UCB using CD93 monoclonal antibodies (mAbs) that recognize different antigenic epitopes remains poorly understood. In this study, we examined the expression of CD93 on lymphocytes, monocytes, and granulocytes from neonatal UCB using four different types of CD93 mAb detection probes, mNI-11, R139, R3, and X-2, using flow cytometric and western blot analyses. We found that CD93, as defined using all four mAbs, was expressed on monocytes and granulocytes in PB mononuclear cells from adult PB and neonatal UCB. On the other hand, we observed for the first time that the expression of CD93 on lymphocytes in neonatal UCB can only be detected using the mNI-11 mAb, established in our laboratory, and not with commercially available CD93 mAbs (R139, R3, and X-2). However, CD93 expression on lymphocytes from normal adults was not detected using any of the four CD93 mAbs. Two-color flow cytometric analyses showed that the CD93 recognized by mNI-11 mAb was expressed on CD3(+) T lymphocytes (mainly CD4(+) helper T lymphocytes), but not on CD19(+) B lymphocytes or on CD8(+) suppressor/cytotoxic T lymphocytes from neonatal UCB. In addition, CD93 was expressed on CD45RA(+) (naive antigen) lymphocytes from neonatal UCB, but not on CD45RO(+) (memory antigen) lymphocytes from neonatal UCB or on CD45RA(+) and CD45RO(+) lymphocytes from normal adult PB. Three-color flow cytometric analysis showed that CD93 was co-expressed on naive T lymphocytes (CD4(+)CD45RA(+)) from neonatal UCB. In a western blot analysis, the CD93 mAb (mNI-11) immunoprecipitated at a molecular weight of 98 kDa, identified as a CD93 molecule, in the CD4(+)CD45RA(+) cells from neonatal UCB but not from adult PB, similar to the results in the human monocyte-like cell line U937 (human CD93-positive cells). Taken together, these results provide the first direct evidence of a novel/naive cell population (CD4(+)CD45RA(+)CD93(+)) in neonatal UCB that may have an important role in cell biology, transplantation, and immature/mature immune responses.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2014
DOI: 10.1007/S00438-013-0792-2
Abstract: In order to investigate the polymorphism of Alu insertions (POALINs) in the HLA region, we genotyped ten Alu loci (AluMICB, AluTF, AluHJ, AluHG, AluHF in the HLA class I region and AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10 in the HLA class II region) to determine their allele frequencies and associations with the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes in the Chinese Han population. Our results showed the ten-loci POALINs varied in frequency between 0.003 and 0.425. By comparing the data of the ten-loci POALIN in Chinese Han with Japanese and Caucasian data, marked differences were observed between the three ethnic groups at the allelic or haplotypic levels. Each POALIN was in significant linkage disequilibrium with a variety of HLA-A, -B, -C and -DRB1 alleles, and was associated with a variety of HLA-A, -B, -C and -DRB1 allele in Chinese Han. This comparative study of multilocus POALINs in the HLA class I and II regions of the Chinese Han population shows that POALINs alone or as haplotypes together with the HLA class I and II alleles are informative genetic markers for the identification of HLA class I and II allele and variations, such as crossing over events within the same and/or different populations.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2007
DOI: 10.1007/S00251-006-0186-2
Abstract: Despite matching donors and recipients for the human leukocyte antigens (HLAs) expressed by the major histocompatibility genomic region of the short arm of chromosome 6, several recipients still develop acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT). This is possibly due to non-HLA gene polymorphisms, such as minor histocompatibility antigens (mHas) and genes coding for cytokines. However, a detailed genetic background for aGVHD has not yet been established. To find novel susceptibility and/or protective loci for aGVHD, a whole genome-wide association study of donors and recipients needs to be performed. As the first step to such a study, we retrospectively analyzed polymorphisms of 155 microsatellite markers spread across the long arm of chromosome 22 in 70 pairs of HLA-matched unrelated BMT donors and recipients. We performed in idual typing and then compared the markers' allele frequencies (1) between all the aGVHD (grades III and IV GVHD) and GVHD-free (grade 0 GVHD) groups in donors and recipients and (2) between the aGVHD and aGVHD-free groups in donor/recipient pairs that were matched and mismatched for the microsatellite marker's allele. Screening of the microsatellite markers revealed five loci with a significant difference between the aGVHD and GVHD-free groups and revealed eight loci on chromosome 22, where the microsatellite allele mismatched markers were associated with aGVHD. This screening analysis suggests that several aGVHD-associated susceptible and protective loci exist on chromosome 22, which may encompass novel gene regions that need to be elucidated for their role in aGVHD.
Publisher: Wiley
Date: 23-08-2021
DOI: 10.1111/TAN.14412
Abstract: Three novel HLA‐DRA alleles, DRA*01:03, DRA*01:04 , and DRA*01:05 alleles with unique amino acid sequences.
Publisher: Wiley
Date: 16-02-2004
Publisher: Springer Science and Business Media LLC
Date: 2005
DOI: 10.1007/S00335-004-2416-Y
Abstract: We have identified and characterized a new gene sequence, TXNRD3NT1, whose transcripts, corresponding to the EST AA430236, were found by Affymetrix DNA chip analysis to be significantly down regulated in affected psoriatic tissue. The full-length cDNA of TXNRD3NT1 was isolated and characterized by combining 5'- and 3'-RACE (rapid lication of cDNA ends) with screening a keratinocyte cDNA library, designing appropriate PCR primers, cloning lified products, sequencing, and sequence analysis. Because part of this gene overlaps the previously described thioredoxin reductase 3 (TXNRD3) gene, we have named it TXNRD3NT1 (TXNRD3 new transcript 1). The full-length TXNRD3NT1 cDNA has 1133 nucleotides with a 251-bp 3-UTRand 2 poly(A)signal variants and 2 poly (A) sites. The TXNRD3NT1 cDNA ORF encodes for 133 amino acids, with the first four residues coding for a tubulin-beta mRNA autoregulation signal. Mapping the cDNA nucleotide sequence to the human genome sequence revealed that the TXNRD3NT1 gene has 4 exons located on Chromosome 3, at position 3q21. Exons 1 and 2 of the TXNRD3NT1 gene overlap with exons 15 and 16 of the thioredoxin reductase 2 gene which has different ORFs to that of TXNRD3NT1. The translation initiation codon ATG was found in exon 3 of the TXNRD3NT1 gene. RT-PCR showed that the full-length variant of the TXNRD3NT1 gene was expressed in only four issues (pancreas, esophagus, bone marrow, and keratinocytes) of the 30 different tissues tested. In most other tissues, an aberrant and truncated form of the transcript (i.e., missing exon 3 and part of exon 4) was detected. The result of a preliminary association study between psoriasis and single microsatellite marker of the TXNRD3NT1 gene suggests that it may not be a significant genetic determinant of psoriasis. However, we cannot exclude the possibility that other sequence variants may still exist within the TXNRD3NT1 gene. Sequence analysis of the TXNRD3NT1 gene from 8 psoriasis patients and 8 healthy controls revealed a number of synonymous SNPs that may be useful markers for future disease association studies.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2010
Publisher: Springer Science and Business Media LLC
Date: 12-1997
DOI: 10.1007/PL00006264
Abstract: Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements, 14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically into two clades which were classified as "preduplication" and "postduplication" clades. Four Alu J elements that are shared by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a "preduplication" clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg) to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to the ergence of the New World primate from the human lineage (35-44 mya). Examination of the paralogous Alu integration sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within the Alu 3'-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended segmental duplication between 44 and 81 million years ago (mya), and that subsequent ersification of both genomic segments occurred because of the mobility and mutation of retroelements such as Alu repeats.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/147064
Abstract: Hexanchiformes is regarded as a monophyletic taxon, but the morphological and genetic relationships between the five extant species within the order are still uncertain. In this study, we determined the whole mitochondrial DNA (mtDNA) sequences of seven sharks including representatives of the five Hexanchiformes, one squaliform, and one carcharhiniform and inferred the phylogenetic relationships among those species and 12 other Chondrichthyes (cartilaginous fishes) species for which the complete mitogenome is available. The monophyly of Hexanchiformes and its close relation with all other Squaliformes sharks were strongly supported by likelihood and Bayesian phylogenetic analysis of 13,749 aligned nucleotides of 13 protein coding genes and two rRNA genes that were derived from the whole mDNA sequences of the 19 species. The phylogeny suggested that Hexanchiformes is in the superorder Squalomorphi, Chlamydoselachus anguineus (frilled shark) is the sister species to all other Hexanchiformes, and the relations within Hexanchiformes are well resolved as Chlamydoselachus , ( Notorynchus , ( Heptranchias , ( Hexanchus griseus , H. nakamurai ))). Based on our phylogeny, we discussed evolutionary scenarios of the jaw suspension mechanism and gill slit numbers that are significant features in the sharks.
Publisher: Wiley
Date: 12-08-2015
DOI: 10.1111/TAN.12637
Abstract: This is the first report on human leukocyte antigen (HLA) allele and haplotype frequencies at three class I loci and two class II loci in unrelated healthy in iduals from two ethnic groups, 170 Burmese and 200 Karen, originally from Burma (Myanmar), but s led while residing in Thailand. Overall, the HLA allele and haplotype frequencies detected by polymerase chain reaction sequence-specific primer (PCR-SSP) at five loci (A, B, C, DRB1 and DRQB1) at low resolution showed distinct differences between the Burmese and Karen. In Burmese, five HLA-B*15 haplotypes with different HLA-A and HLA-DR/DQ combinations were detected with three of these not previously reported in other Asian populations. The data are important in the fields of anthropology, transplantation and disease-association studies.
Publisher: Elsevier BV
Date: 09-1981
Publisher: Wiley
Date: 09-1990
Abstract: A retrospective study was undertaken to determine the prevalence of human papillomavirus (HPV) infections in routine Papanicolaou (Pap) smears collected by general practitioners from Western Australian women in each of the years 1972, 1982, and 1987. HPV infection was detected by cytology, dot-blot hybridization, or polymerase chain reaction (PCR). It was found that the prevalence of HPV infection remained unchanged over the 15 year study period, was independent of age, and was associated with normal cytology at a rate far greater than previously recognized. Indeed, the prevalence of cervical intraepithelial neoplasia (CIN) lesions, as detected by cytology, was 3.0% in 1972 and 3.8% in 1982 and 1987. The prevalence of HPV infection, detected as koilocytosis or parakeratosis, was 6.5%, 6.8%, and 5.3% in smears collected in 1972, 1982, and 1987, respectively, from 1,800 women. In 237 cytologically normal smears reprocessed for HPV-DNA studies, the prevalence of HPV 16 was determined to be 15.6%, 11.2%, and 17.8% in 1972, 1982, and 1987, respectively, as determined by dot-blot hybridization. However, the PCR detected HPV 16 in an additional 55.5%, 62.9%, and 57.0% of cytologically normal and dot-blot negative smears. The prevalence of HPV 16 infection in cytologically normal smears was estimated to be 71.0%, 74.1%, and 74.8% in 1972, 1982, and 1987, respectively, by combining the HPV 16 dot-blot and PCR-positive results. The high prevalence of HPV 16 in cytologically normal Pap smears suggests that infection with HPV 16, as detected by PCR lification, does not place women in a high-risk category for cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 21-04-2011
DOI: 10.1111/J.1399-0039.2011.01669.X
Abstract: A simple and novel genotyping method was developed to detect alleles at the swine leukocyte antigen (SLA)-DRB1 and -DQB1 class II loci by using polymerase chain reaction (PCR)-fluorescently labeled sequence-specific oligonucleotide probes (SSOPs) and Luminex 100 xMAP detection. The PCR-SSOP-Luminex method exhibited accuracy of 95% for both SLA-DRB1 and -DQB1 in 6 homozygous and 16 heterozygous pig s les as confirmed by sequencing the PCR products of the same s les. In addition, 12 low-resolution SLA class II haplotypes consisting of 7 and 9 DRB1 and DQB1 alleles were identified, respectively, in one population of 283 Landrace pigs. This genotyping method facilitates the rapid and accurate identification of two- or four-digit alleles at the SLA-DRB1 and -DQB1 loci.
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000084952
Abstract: Most polymorphic Alu insertions (POALINs) belong to a subgroup of the Alu multicopy retrotransposon family of short interspersed nucleotide elements (SINEs) that are categorized as AluYb8 and AluYa5. The number of AluYb8/AluYa5 members (∼4,492 copies) is significantly less than the ∼one million fixed Alu copies per human genome. We have studied the presence of POALINs within the Major Histocompatibility Complex (MHC) class I region on the short arm of chromosome 6 (6p21.3) because this region has a high gene density, many genes with immune system functions, large sequence variations and ersity, duplications and redundancy, and a strong association with more than 100 different diseases. Since little is known about POALINs within the MHC genomic region, we undertook to identify some of the members of the AluYb8/AluYa5 subfamily and to study their frequency of distribution and genetic characteristics in different populations. As a result of our comparative genomic analyses, we identified the insertion sites for five POALINs distributed within the MHC class I region. This brief review outlines the locations of the insertions and sequence features of the five MHC POALINs, their single site and haplotype frequencies in different geographic populations, and their association with different HLA class I genes and disease. We show that the MHC POALINs have a potential value as lineage and linkage markers for the study of human population genetics, disease associations, genomic ersity and evolution.
Publisher: Wiley
Date: 02-1987
DOI: 10.1038/ICB.1987.9
Abstract: The presence of human papillomavirus (HPV) types 11, 16 and 18 in 77 biopsies of cervical intraepithelial neoplasia (dysplasia) and carcinoma of the uterine cervix of a s le of women from Western Australia was examined using "Southern" blot hybridisation. HPV-DNA was found in 17 of the 23 dysplasias and 43 of the 54 invasive carcinomas examined but not in the 5 biopsies obtained from areas assessed as normal by colposcopy and histology. Five of 11 biopsies of mild to moderate dysplasias contained HPV type 11 (HPV-11), 2 HPV-16 and 1 HPV-18. Of 12 severe dysplasias/carcinoma in situ, 2 contained HPV-11, 4 HPV-16 and 2 HPV-18. One biopsy contained both HPV-11 and HPV-16. Of 45 squamous cell carcinomas examined for HPV-DNA, 24 contained HPV-16, 5 HPV-11 and 1 HPV-18. Both HPV-11 and HPV-16 were found in 6 of the squamous cell carcinomas and 2 contained both HPV-16 and HPV-18. Of 6 adenosquamous carcinomas examined, 3 contained HPV-DNA, 2 with HPV-16 and 1 with HPV-11. HPV types 16 or 18 were also found in 2 of 3 adenocarcinomas. This study shows a strong association between the papillomavirus and uterine cervical cancer in a s le of women from Western Australia. HPV-16 was more frequently associated with severe dysplasia and cancer than with mild or moderate dysplasia supporting the view that this HPV genotype may have a greater oncogenic potential than HPV-11.
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000084951
Abstract: The genomic sequences within the alpha-block (∼288–310 kb) of the human and chimpanzee MHC class I region contains ten MHC class I genes and three MIC gene fragments grouped together within alternating duplicated genomic segments or duplicons. In this study, the chimpanzee and human genomic sequences were analyzed in order to determine whether the remnants of the ERVK9 and other retrotransposon sequences are useful genomic markers for reconstructing the evolutionary history of the duplicated MHC gene families within the alpha-block. A variety of genes, pseudogenes, autologous DNA transposons and retrotransposons such as Alu and ERVK9 were used to categorize the ten duplicons into four distinct structural groups. The phylogenetic relationship of the ten duplicons was examined by using the neighbour joining method to analyze transposon sequence topologies of selected Alu members, LTR16B and Charlie9. On the basis of these structural groups and the phylogeny of the duplicated transposon sequences, a duplication model was reconstructed involving four multipartite tandem duplication steps to explain the organization and evolution of the ten duplicons within the alpha-block of the chimpanzee and human. The phylogenetic analysis and inferred duplication history suggests that the Patr/HLA-F was the first MHC class I gene to have been fixed and not required as a precursor for further duplication within the alpha-block of the ancestral species.
Publisher: Microbiology Society
Date: 04-1989
DOI: 10.1099/0022-1317-70-4-1005
Abstract: Papillomas, carcinomas in situ and squamous cell carcinomas were induced using ultraviolet irradiation in the hairless mouse strain Mus musculus HRA/Skh. DNA extracted from biopsies was examined using Mastomys natalensis papillomaviral DNA as a hybridization probe at reduced stringency. Sequences homologous to the probe were detected in 16 of 24 papillomas, five of five carcinomas in situ and six of 38 squamous cell carcinomas. A number of tumour DNAs (16/33) also hybridized with mixed DNAs of human papillomavirus types 11, 13, 16 and 18 at reduced stringency. This suggests a role for the hairless mouse as a laboratory model for the study of the involvement of papillomaviruses in malignant transformations.
Publisher: Springer Japan
Date: 2000
Publisher: Springer Japan
Date: 2000
Publisher: Springer Japan
Date: 2000
Publisher: Wiley
Date: 04-2006
DOI: 10.1111/J.1399-0039.2006.00577.X
Abstract: Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or ersity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 in iduals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.
Publisher: Springer Science and Business Media LLC
Date: 05-2012
Publisher: Springer Science and Business Media LLC
Date: 20-02-2010
DOI: 10.1007/S00251-010-0427-2
Abstract: Polymorphic insertion frequencies of the retrotransposons known as the "SVA" elements were investigated at four loci in the MHC class I genomic region to determine their allele and haplotype frequencies and associations with the HLA-A, -B or -C genes for 100 Japanese, 100 African Americans, 174 Australian Caucasians and 66 reference cell lines obtained from different ethnic groups. The SVA insertions representing different subfamily members varied in frequency between none for SVA-HF in Japanese and 65% for SVA-HB in Caucasians or African Americans with significant differences in frequencies between the three populations at least at three loci. The SVA loci were in Hardy-Weinberg equilibrium except for the SVA-HA locus which deviated significantly in African Americans and Caucasians possibly because of a genomic deletion of this locus in in iduals with the HLA-A*24 allele. Strong linkage disequilibria and high percentage associations between the human leucocyte antigen (HLA) class I gene alleles and some of the SVA insertions were detected in all three populations in spite of significant frequency differences for the SVA and HLA class I alleles between the three populations. The highest percentage associations (>86%) were between SVA-HB and HLA-B*08, -B*27, -B*37 to -B*41, -B*52 and -B*53 SVA-HC and HLA-B*07 SVA-HA and HLA-A*03, -A*11 and -A*30 and SVA-HF and HLA-A*03 and HLA-B*47. From pairwise associations in the three populations and the homozygous cell line results, it was possible to deduce the SVA and HLA class I allelic combinations (haplotypes), population differences and the identity by descent of several common HLA-A allelic lineages.
Publisher: Wiley
Date: 07-1990
Abstract: DNA dot blot hybridization was used for the detection of human papillomavirus (HPV) types 6, 11, 16, and 18 in reprocessed routinely collected Papanicolaou smears. DNA was extracted from the smears with alkaline lysis and applied onto a nitrocellulose filter. The specificity and sensitivity of the dot blot hybridization on reprocessed Papanicolaou smears were confirmed by Southern blot analysis of selected s les, using CaSki, SiHa cell lines as positive controls and HF 32 as negative controls. From 42 normal smears and 44 abnormal smears with koilocytosis present, 9 (21%) and 43 (98%), respectively, were positive for HPV 6/11/16 or 18. These results show that reprocessed Papanicolaou smears in combination with DNA hybridization have potential application in retrospective studies on the prevalence and distribution of HPV infection.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2005
DOI: 10.1007/S00251-004-0755-1
Abstract: Salmonid fishes are among the few animal taxa with a probable recent tetraploid ancestor. The present study is the first to compare large (>100 kb) duplicated genomic sequence fragments in such species. Two contiguous stretches with major histocompatibility complex (MHC) class I genes were detected in a rainbow trout BAC library, mapped and sequenced. The MHC class I duplicated regions, mapped by fluorescence in situ hybridization (FISH), were shown to be located on different metaphase chromosomes, Chr 14 and 18. Gene organization in both duplications is similar to that in other fishes, in that the class I loci are tightly linked with the PSMB8, PSMB9, PSMB10 and ABCB3 genes. Whereas one region, Onmy-IA, has a classical MHC class I locus (UBA), Onmy-IB encodes only non-classical class Ib proteins. The nucleotide ersity between the Onmy-IA and Onmy-IB noncoding regions is about 14%. This suggests that the MHC class I duplication event has occurred about 60 mya close to the time of an hypothesized ancestral tetraploid event. The present article is the first convincing report on the co-existence of two closely related MHC class I core regions on two different chromosomes. The interchromosomal duplication and the homology levels are supportive of the tetraploid model.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2012
Publisher: Bioscientifica
Date: 10-1988
Abstract: Commercial preparations of serum albumin from six species can markedly enhance the prolactin-independent induction of α-lactalbumin in mammary explants from pregnant rats, and evoke such induction in the tissue from virgin rats. These effects are similar to those of epidermal growth factor (EGF) reported previously. The stimulatory activity of bovine serum albumin (BSA) resides in a putative impurity in the albumin. Charcoal extraction and gel filtration of the BSA results in complete loss of activity. Of the five milk protein mRNAs studied, only α-lactalbumin mRNA is induced by insulin, glucocorticoid and serum albumin in the absence of prolactin. Despite these similarities, the biological effects of serum albumin and EGF on mammary tissue erge in some respects. They appear to operate by different mechanisms since their effects on the rat system are additive. Furthermore, while both inhibit prolactin-mediated induction of α-lactalbumin in rabbit mammary explants, cortisol converts EGF into a stimulatory agent, but merely blocks the inhibitory effect of serum albumin. The results emphasize that commercial serum albumin is not to be regarded simply as an inert protein additive to culture media. J. Endocr . (1988) 119, 133–139
Publisher: Springer Science and Business Media LLC
Date: 08-2009
DOI: 10.1007/S00251-009-0390-Y
Abstract: Cynomolgus macaques (Macaca fascicularis, Mafa) have emerged as important animal models for biomedical research, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphism or ersity of the polygenetic Mafa class I A loci is limited in comparison to the more commonly studied rhesus macaque Mafa class I A loci. Therefore, in this paper, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-A1 among three native Southeast Asian populations (Indonesian, Vietnamese, and Filipino) and to investigate how the allele differences between macaques and humans might have evolved to affect their respective immune responses, we identified 83 Mafa-A loci-derived alleles by DNA sequencing of which 66 are newly described. Most alleles are unique to each population, but seven of the most frequent alleles were identical in sequence to some alleles in other macaque species. We also revealed (1) the large and dynamic genetic and structural differences and similarities in allelic variation by analyzing the population allele frequencies, Hardy-Weinberg's equilibrium, heterozygosity, nucleotide ersity profiles, and phylogeny, (2) the difference in genetic structure of populations by Wright's FST statistic and hierarchical analysis of molecular variance, and (3) the different demographic and selection pressures on the three populations by performing Tajima's D test of neutrality. The large level of ersity and polymorphism at the Mafa-A1 was less evident in the Filipino than in the Vietnam or the Indonesian populations, which may have important implications in animal capture, selection, and breeding for medical research.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2009
DOI: 10.1007/S00251-009-0363-1
Abstract: The Major Histocompatibility Complex (Mhc) class II DRB locus of vertebrates is highly polymorphic and some alleles may be shared between closely related species as a result of balancing selection in association with resistance to parasites. In this study, we developed a new set of PCR primers to lify, clone, and sequence overlapping portions of the Mhc class II DRB-like gene from the 5'UTR end to intron 3, including exons 1, 2, and 3 and introns 1 and 2 in four species (20 Humboldt, six African, five Magellanic, and three Galapagos penguins) of penguin from the genus Spheniscus (Sphe). Analysis of gene sequence variation by the neighbor-joining method of 21 Sphe sequences and 20 previously published sequences from four other penguin species revealed overlapping clades within the Sphe species, but species-specific clades for the other penguin species. The overlap of the DRB-like gene sequence variants between the four Sphe species suggests that, despite their allopatric distribution, the Sphe species are closely related and that some shared DRB1 alleles may have undergone a trans-species inheritance because of balancing selection and/or recent rapid speciation. The new primers and PCR assays that we have developed for the identification of the DRB1 DNA and protein sequence variations appear to be useful for the characterization of the molecular evolution of the gene in closely related Penguin species and might be helpful for the assessment of the genetic health and the management of the conservation and captivity of these endangered species.
Publisher: MDPI AG
Date: 26-07-2019
DOI: 10.3390/CELLS8080783
Abstract: The effects of swine leukocyte antigen (SLA) molecules on numerous production and reproduction performance traits have been mainly reported as associations with specific SLA haplotypes that were assigned using serological typing methods. In this study, we intended to clarify the association between SLA class II genes and reproductive traits in a highly inbred population of 187 Microminipigs (MMP), that have eight different types of SLA class II haplotypes. In doing so, we compared the reproductive performances, such as fertility index, gestation period, litter size, and number of stillbirth among SLA class II low resolution haplotypes (Lrs) that were assigned by a polymerase chain reaction-sequence specific primers (PCR-SSP) typing method. Only low resolution haplotypes were used in this study because the eight SLA class II high-resolution haplotypes had been assigned to the 14 parents or the progenitors of the highly inbred MMP herd in a previous publication. The fertility index of dams with Lr-0.13 was significantly lower than that of dams with Lr-0.16, Lr-0.17, Lr-0.18, or Lr-0.37. Dams with Lr-0.23 had significantly smaller litter size at birth than those with Lr-0.17, Lr-0.18, or Lr-0.37. Furthermore, litter size at weaning of dams with Lr-0.23 was also significantly smaller than those dams with Lr-0.16, Lr-0.17, Lr-0.18, or Lr-0.37. The small litter size of dams with Lr-0.23 correlated with the smaller body sizes of these MMPs. These results suggest that SLA class II haplotypes are useful differential genetic markers for further haplotypic and epistatic studies of reproductive traits, selective breeding programs, and improvements in the production and reproduction performances of MMPs.
Publisher: Wiley
Date: 02-1999
DOI: 10.1111/J.1600-065X.1999.TB01399.X
Abstract: The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very erse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid ersification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.
Publisher: Informa UK Limited
Date: 1997
Publisher: Springer Science and Business Media LLC
Date: 12-1987
DOI: 10.1007/BF00145653
Abstract: Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. In westernized societies, it is the underlying cause of about 50% of all deaths. Epidemiological studies have revealed several important environmental and genetic risk factors associated with atherosclerosis. Progress in defining the cellular and molecular interactions involved, however, has been hindered by the disease's aetiological complexity. Over the past decade, the availability of new investigative tools, including genetically modified mouse models of disease, has resulted in a clearer understanding of the molecular mechanisms that connect altered cholesterol metabolism and other risk factors to the development of atherosclerotic plaque. It is now clear that atherosclerosis is not simply an inevitable degenerative consequence of ageing, but rather a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Humana Press
Date: 1999
DOI: 10.1385/0-89603-518-2:119
Abstract: Polymerase chain reaction (PCR) is an important qualitative procedure in the routine microbiology laboratory for detecting the presence or absence of potentially harmful microorganisms in clinical specimens (1,2). The use of PCR to quantify an infectious agent in a clinical specimen (e.g., viral or bacterial load) is advantageous for monitoring disease progression and efficacy of treatment, for differentiating between asymptomatic and symptomatic infection, or for quality control of false positive s les. End-point titration-PCR (ET-PCR) is a simple method for differentiating between the presence of low, medium, or high amounts of viral, fungal, or bacterial DNA in a test s le. Basically, the qualitative PCR method (3) is used in an ET-PCR to lify a specific target sequence in serial dilutions of a DNA s le (4). The limit of detection of the lified product, which is the end-point dilution or titer, is the quantitative index for the DNA target in the s le. End-point titers obtained by ET-PCR have been shown to increase proportionally with increasing amounts of standard DNA (4). The result of an ET-PCR can be presented as a titer, dilution, DNA copy number, or amount of a specific DNA sequence relative to an external standard or as relative differences between s les. On this basis, ET-PCR has been used to quantitate the presence of viral and bacterial DNA in clinical specimens (4-10). The ET-PCR method described here is for the quantitation of cytomegalovirus (CMV) DNA in leukocytes (4).
Publisher: Wiley
Date: 10-07-2016
DOI: 10.1111/IMM.12624
Publisher: Springer Science and Business Media LLC
Date: 09-03-2013
DOI: 10.1007/S00251-013-0690-0
Abstract: Our aim was to test and develop the use of loop-mediated isothermal lification (LAMP) for HLA-DRB1 genotyping. Initially, we found that the conventional LAMP protocols produced non-specific and variable lification results depending on the s le DNA conditions. Experiments with different concentrations of DNase in the reaction mixture with and without T4 DNA ligase-treated s les suggested that the strand displacement activity of DNA polymerase in LAMP, at least in part, started from randomly existing nicks because T4 DNA ligase treatment of s le DNA resulted in no lification. Such non-specific lification due to the randomly existing nicks was improved specifically by the addition of RecA of Escherichia coli and a restriction enzyme, for ex le, PvuII, to the reaction mixture. We applied the modified LAMP (mLAMP) (1) to detect specific HLA-DRB1 alleles by using only specific primers for lification or (2) for genotyping in multiple s les with a multi-probe typing system. In the latter case, HLA-DRB1 genotyping was developed by combining the mLAMP with licon capture using polymorphic region-specific probes fixed onto the bottom of the wells of a 96-well plate and the captured licons visualized as a black spot at the bottom of the well. The multi-probe human leukocyte antigen (HLA) typing method and the specific HLA allele detection method could be applied for point-of-care testing due to no requirement for specific and expensive instruments.
Publisher: Figshare
Date: 2011
Publisher: Wiley
Date: 08-2001
DOI: 10.1034/J.1399-0039.2001.580202.X
Abstract: Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR- lified product of 9.5 kb which was then used as a template for nested PCR to give a final lified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.
Publisher: Wiley
Date: 20-03-2018
DOI: 10.1111/IJI.12418
Abstract: The high degree of polymorphism of the HLA system provides suitable genetic markers to study the ersity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low-resolution PCR-SSP genotyping of three HLA class I loci at HLA-A, -B and -C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE. A total of 54 HLA allele lineages were detected the most frequent low-resolution allele lineages at each HLA locus were A*02 (0.268), B*51 (0.163) and C*07 (0.216). The inferred estimates for the two most frequent HLA-A and HLA-B haplotypes were HLA-A*02 ~ HLA-B*50 (0.070) and HLA-A*02 ~ HLA-B*51 (0.051), and the most frequent 3-locus haplotype was HLA-A*02 ~ HLA-B*50 ~ HLA-C*06 (0.068). The HLA allele lineage frequencies of the UAE Arabs were compared to those previously reported for 70 other world populations, and a strong genetic similarity was detected between the UAE Arabs and the Saudi Arabians from the west with evidence of a limited gene flow between the UAE Arabs and Pakistani across the Gulf from the east, and the UAE Arabs and Omani from the south of the Gulf Peninsula.
Publisher: Elsevier BV
Date: 07-1983
DOI: 10.1016/0006-291X(83)91638-8
Abstract: It is demonstrated that the accumulation of 42 K casein mRNA in mammary tissue from adrenalectomized, virgin rats is almost 20x higher in the presence of exogenous hydrocortisone than in its absence. Accumulation of 25 K casein mRNA in this tissue is totally dependent on the steroid. The results indicate a much greater dependency on hydrocortisone than was appreciated previously, and also show that this dependency does not reflect a loss of cell viability in the absence of the steroid.
Publisher: Japanese Society of Internal Medicine
Date: 2014
DOI: 10.2169/INTERNALMEDICINE.53.1320
Abstract: Progressive external ophthalmoplegia (PEO) is one of a number of major types of mitochondrial disorders. Most sporadic PEO patients have a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in the mitochondria in skeletal muscles. We herein analyzed mtDNA deletions using sub-cloning and Sanger sequencing of PCR products in a 31-year-old Japanese man with multiple symptoms, including PEO, muscle weakness, hearing loss, leukoencephalopathy and hypogonadism. A large number of multiple deletions was detected, as well as four kinds of deletion breakpoints identified in different locations, including m.3347_12322, m.5818_13964, m.5829_13964 and m.5837_13503.
Publisher: Elsevier BV
Date: 06-1992
DOI: 10.1016/0378-1135(92)90125-D
Abstract: Small hyperkeratotic and ulcerated lesions and clinical cancers were isolated from the perineal region of sheep and examined for evidence of papillomavirus infection by various criteria including gross morphology, histology, immunohistochemistry and DNA hybridisation. No specific diagnostic features of papillomaviral infection by immunohistochemistry were found, although some lesions showed gross morphological and histological features similar to papillomaviral effect in other species. DNA hybridisation analysis, using human papillomaviral type 11, 13, 16 and 18 DNA probes under conditions of reduced stringency (Tm-40 degrees C), detected homologous sequences in two thirds of the biopsies examined. These homologous sequences occurred in benign hyperkeratosis as well as invasive squamous cell carcinomas but were much more frequently isolated from carcinomas. This finding suggests that a papillomavirus is associated with the development of squamous cell carcinomas of the perineum of sheep.
Publisher: Elsevier BV
Date: 1987
DOI: 10.3109/00313028709065144
Abstract: Cervical biopsies obtained by colposcopic direction from 358 women were histologically examined for squamous dysplasia (cervical intra-epithelial neoplasia CIN) and human papillomavirus (HPV) infection. Of the 358 biopsies, 136 were stained by an immunoperoxidase method using an antiserum against genus-specific (common) antigen of bovine papillomavirus. HPV antigens were detected in 40% of biopsies showing definite histological evidence of HPV effect, and in 7.9% and 2.6% of those with possible or no HPV effect, respectively. HPV effect was commonly seen in association with CIN. The frequency of histological evidence of HPV effect and positive immunoperoxidase staining decreased with increasing grades of CIN. HPV antigen was found in 57% of areas of HPV change with minor atypia, 34% of zones of CIN I and in only 8% of zones of CIN II. No antigenic staining or definite histological evidence of HPV effect was observed within areas of CIN III. Antigen was generally confined to the nuclei of superficial koilocytes, cells with lesser degrees of perinuclear clearing and parakeratotic cells. These results how a strong association between HPV infection and precancerous lesions of the uterine cervix and are consistent with the hypothesis that production of the HPV structural antigen requires a high degree of squamous cell maturation. The immunoperoxidase findings and the histopathological observations support the view that HPV change and dysplasia are part of a morphological continuum in which the cytopathic effect of HPV is expressed mainly in lower grades of dysplasia.
Publisher: Oxford University Press (OUP)
Date: 07-2006
DOI: 10.1534/GENETICS.106.057034
Abstract: A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and nonhuman primate haplotypes allowed an analysis of single nucleotide variations (SNV) across this entire segment. This ersity was not evenly distributed. It was rather concentrated within two gene-rich clusters. These were each centered, but importantly not limited to, the antigen-presenting HLA-A and HLA-B/-C loci. Rapid evolution of MHC-I alleles, as evidenced by an unusually high number of haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs within the classical MHC-I, seems to have not only hitchhiked alleles within nearby genes, but also hitchhiked deleterious mutations in these same unrelated loci. The overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species ersity tsSNV included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2022
DOI: 10.1007/S00251-021-01234-5
Abstract: The dog leukocyte antigen (DLA) class I genomic region is located on chromosome 12, and the class I genomic region is composed of at least two distinct haplotypic gene structures, DLA-88-DLA-12 and DLA-88-DLA-88L. However, detailed information of the genomic differences among DLA-88, DLA-12, and DLA-88L are still lacking at the full-length gene level, and therefore, DLA allelic sequences classified for each of these loci are limited in number so far. In this study, we determined the DNA sequence of a 95-kb DLA class I genomic region including DLA-88, DLA-12/88L, and DLA-64 with three DLA homozygous dogs and of 37 full-length allelic gene sequences for DLA-88 and DLA-12/88L loci in 26 DLA class I homozygous dogs. Nucleotide ersity profiles of the 95-kb regions and sequence identity scores of the allelic sequences suggested that DLA-88L is a hybrid gene generated by interlocus and/or intralocus gene conversion between DLA-88 and DLA-12. The putative minimum conversion tract was estimated to be at least an 850-bp segment in length located from the 5´flanking untranslated region to the end of intron 2. In addition, at least one DLA-12 allele (DLA-12*004:01) was newly generated by interlocus gene conversion. In conclusion, the analysis for the occurrence of gene conversion within the dog DLA class I region revealed intralocus gene conversion tracts in 17 of 27 DLA-88 alleles and two of 10 DLA-12 alleles, suggesting that intralocus gene conversion has played an important role in expanding DLA allelic variations.
Publisher: Wiley
Date: 12-1981
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.1007/S00251-003-0627-0
Abstract: Genome analysis of the swine leukocyte antigen ( SLA) region is needed to obtain information on the MHC genomic sequence similarities and differences between the swine and human, given the possible use of swine organs for xenotransplantation. Here, the genomic sequences of a 433-kb segment located between the non-classical and classical SLA class I gene clusters were determined and analyzed for gene organization and contents of repetitive sequences. The genomic organization and ersity of this swine non-class I gene region was compared with the orthologous region of the human leukocyte antigen ( HLA) complex. The length of the fully sequenced SLA genomic segment was 433 kb compared with 595 kb in the corresponding HLA class I region. This 162-kb difference in size between the swine and human genomic segments can be explained by indel activity, and the greater variety and density of repetitive sequences within the human MHC. Twenty-one swine genes with strong sequence similarity to the corresponding human genes were identified, with the gene order from the centromere to telomere of HCR - SPR1 - SEEK1 - CDSN - STG - DPCR1 - KIAA1885 - TFIIH - DDR - IER3 - FLOT1 - TUBB - KIAA0170 - NRM - KIAA1949 - DDX16 - FLJ13158 - MRPS18B - FB19 - ABCFI - CAT56. The human SEEK1 and DPCR1 genes are pseudogenes in swine. We conclude that the swine non-class I gene region that we have sequenced is highly conserved and therefore homologous to the corresponding region located between the HLA-C and HLA-E genes in the human.
Publisher: Springer Science and Business Media LLC
Date: 03-1996
DOI: 10.1007/BF02660066
Publisher: Elsevier BV
Date: 1982
Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1016/S1471-4906(01)02155-X
Abstract: Here, we compare the architecture of membrane receptors with extracellular Ig-like domains located within the leukocyte Ig-like receptor complex (LRC) of humans and mice. The receptors can be classified broadly into four groups, based on the homology of their Ig-like domains and gene architecture. Receptors in the first group are characterized by the presence of the Ig constant type 2-1 (IgC2-1) and variant Ig (vlg) domains, and include the leukocyte Ig-like receptors (LILRs) and murine paired Ig-activating receptors (PIRs). The second group of receptors possess an IgC2-2 domain and comprise the killer-cell Ig-like receptors (KIRs) and platelet collagen receptor glycoprotein VI (GPVI). The third group consists of receptors with IgC2-1, and IgC2-3 or IgC2-4 domains, and includes the receptor for IgA Fc (FCAR), NKp46 and murine Ly94. The fourth group, with a single extracellular IgC2-1 domain, consists of the leukocyte-associated Ig-like receptors (LAIRs). The genomic organization of and evolutionary associations between these receptors and their domains are examined.
Publisher: Wiley
Date: 04-1999
DOI: 10.1046/J.1365-2370.1999.00154.X
Abstract: MIC molecules belong to the immunoglobulin superfamily, are encoded within the MHC region and are recognized by γ/δ T‐cell receptors. In humans, at least two functional genes (MIC‐A* and MIC‐B*) and two pseudogenes (MIC‐C* and MIC‐D*) exist. Functional MIC gene copies are characterized by a high degree of polymorphism, while pseudogenes bear several debilitating mutations either in the putative extracellular region or in the transmembrane region of the molecule. In this study we sequenced these segments of MIC genes in seven non‐human primates in order to determine whether debilitating mutations were present. All the MIC primate genes studied were highly homologous to their human counterparts, and cystein residues involved in the maintenance of the immunoglobulin‐like structure were highly conserved. Furthermore, none of the MIC genes studied contained stop codons in the extracellular or transmembrane segments of the molecule, which suggests that at least one functionnal gene copy exists in non‐human primates. A distinct family of MHC immunoglobulin‐like genes was recently identified within the MHC class I region in humans ( Bahram et al. , 1994 Leelayuwat et al. , 1994 ). Members of this MIC (MHC class I chain related) gene family belong to the immunoglobulin superfamily. Similar to classical class I MHC genes, they are characterized by three distinct extracellular domains (α1–3), a transmembrane (TM) segment and a cytoplasmic segment, each encoded by a separate exon ( Bahram et al. , 1994 Bahram et al. , 1996 ). Other similarities between MIC genes and classical MHC genes include a high degree of polymorphism ( Fodil et al. , 1996 Pellet et al. , 1997 ) and recognition by T‐cell receptors ( Groh et al. , 1998 ). These findings suggest that the putative MIC‐A* chain has evolved for a function that is related to, but quite distinct from, that of typical MHC class I chains. Southern blot analysis showed that members of the MIC family exist in most mammalian species ( Bahram et al. , 1994 ). Nevertheless it is still unclear whether functional copies of these genes exist in these species, since MIC pseudogenes (MIC‐C* and MIC‐D*) also exist in humans. Usually, these MIC pseudogenes bear several stop codons in the putative extracellular or TM segments of the gene. In this report, we sequenced the α1, α 2, α 3 and, when possible, TM segments of one in idual’s MIC genes for three Hominidae, three Cercopithecidae and one Hylobatidae species in order determine whether debilitating mutations were present in these exons. Genomic DNA was graciously provided by Professor Barré Sinoussi (Institut Pasteur, Paris, France). The MIC variants were identified by direct sequencing of polymerase chain reaction (PCR) lified gene segments including the α1 (exon 2), α2 (exon 3), α3 (exon 4) and TM exons, as previously described for human MIC‐A* genes ( Fodil et al. 1996 ). The sequences were obtained by using the Dye Primer Sequencing kit (ABI, USA) which enabled us to distinguish the heterozygoous positions in 99% of cases. When heterozygosity was detected, PCR products were subcloned in a plasmid vector (TA Cloning kit Invitrogen, the Netherlands). Several clones were sequenced separately until the definitive sequence of both alleles was obtained. Optimal alignment between primate MIC genes and the human MIC‐A* gene is shown in Fig. 1 . . Extracellular domains of MIC molecules in non‐human primates compared to human MIC‐A*001 (EMBL/GenBank accession number U56940). Dashes indicate amino acid identity, and arrows indicate the cystein residues involved in the maintenance of the immunoglobulin‐like structure. image As expected, the MIC sequences obtained from Hominidae species showed a high degree of homology to their human counterparts, varying between 86 and 97% ( Fig. 1 ). For all Hominidae species, we also obtained the sequence of the TM segment (data not shown), where stop codons occur in human MIC‐A* genes. We did not find any stop codon in any exons sequenced. Furthermore, none of the four cysteins involved in the maintenance of the immunoglobulin‐like structure of the molecule was replaced by other amino acid residues. Among the DNAs analysed, only the Pongo pygmaeus (orang utan) and the Hylobate Par (gibbon) proved to be heterozygous, which suggests that, as in humans, the MIC gene could be polymorphic in these species. For most of the non‐Hominidae species analysed (gibbon, Cercopithecus patas (patas) and Papio sp . (baboon)), optimal alignments suggest that the coding sequences are shorter than in humans. However, as in the Hominidae, the immunoglobulin‐like structure seems preserved since cysteins at positions 96, 164, 202 and 259 were not replaced by other residues even in regions of the molecule that had an important interspecies polymorphism (position 164). These data show that at least one functional MIC gene copy without debilitating mutations in regions affected by this type of modification in human MIC pseudogenes exists. Furthermore, as in humans, for some species these genes are polymorphic and there seems to be a strong evolutionary pressure for the maintenance of an immunoglobulin‐like structure for these molecules. Taken together, these data provide evidence that MIC genes are probably functional and play an important role in host defence in non‐human primates. Further studies investigating the expression of these molecules in these species will be necessary to provide definitive support for this hypothesis.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.VETIMM.2012.05.005
Abstract: The expression of the major histocompatibility complex (MHC) classical class I genes is important for the adaptive immune response to target virus-infected cells and cancer cells. The up-regulation of the MHC is achieved by hormonal/cytokine signals including IFN-γ-inducible elements. The swine leukocyte antigen (SLA), the MHC class I region of pigs, consists of the duplicated classical class I genes, SLA-1, SLA-2 and SLA-3, but the molecular mechanisms involved in their up-regulation after T cell stimulation have not been fully elucidated. In order to better understand some of the putative regulatory mechanisms of SLA class I gene expression in activated T cells, we examined the coordinated expression of the SLA classical class I, IFN-γ and interferon regulatory factor-1 (IRF-1) genes in the peripheral blood mononuclear cells (PBMCs) of SLA homozygous Clawn miniature swine stimulated for 72 h with either IFN-γ or an enterotoxin produced by Staphylococcus aureus. This enterotoxin, toxic shock syndrome-1 (TSST-1), is known to act as a superantigen (sAG) to activate the T cells in various vertebrate species. We showed by using mAbs and flow cytometry that the CD4(+)CD25(+) cell number of swine PBMCs was also increased by TSST-1 and to a lesser degree by IFN-γ. Time course analyses of the expression of the IFN-γ, IRF-1 and the three classical class I genes, SLA-1, SLA-2, and SLA-3, in PBMCs by quantitative real-time PCR revealed a transitory response to TSST-1 or IFN-γ stimulation. The IFN-γ mRNA levels in the PBMCs were continuously up-regulated over the first 48 h by TSST-1 or IFN-γ. In contrast, SLA class I expression moderately increased at 24h and then decreased to a baseline level or less at 72 h of IFN-γ or TSST-1 stimulation. The three classical SLA class I genes showed similar expression kinetics, although SLA-3 mRNA level was consistently lower than those of SLA-1 and -2. The expression of IRF-1, a modulator of SLA expression, showed similar kinetics to those of the three classical SLA class I genes. The expression profiles detected by flow cytometry of the SLA molecules on the cell surface of PBMCs were maintained at a consistently high level during cell stimulation with either TSST-1 or IFN-γ, which was distinct from the kinetics of mRNA expression. These results showed that miniature swine SLA class I mRNA expression was effectively and equally up-regulated among the three loci and coordinately with IRF-1 gene expression after stimulation of T cell activation by sAG or IFN-γ.
Publisher: Elsevier BV
Date: 1986
DOI: 10.3109/00313028609087555
Abstract: A study was undertaken to determine the relative sensitivities of the peroxidase-antiperoxidase (PAP) and avidin-biotin complex (ABC) methods for the detection of human papillomavirus (HPV) antigens in acetic acid-ethanol fixed paraffin-embedded cervical tissue. Tissue sections prepared from 14 women suspected to have HPV infections with either atypia or dysplasia were stained immunohistochemically using an antiserum against genus-specific (common) antigen of bovine papillomavirus. Detection of HPV antigen was approximately twice as frequent by the ABC method as by the PAP method. Of the 14 cases studied, 43% were found to be HPV positive by the PAP method whereas 79% were HPV positive by the ABC method. In addition, the number of cells found to be HPV positive by the ABC method was approximately double the number by the PAP method.
Publisher: Informa UK Limited
Date: 10-2007
DOI: 10.1128/MCB.00479-07
Publisher: The American Association of Immunologists
Date: 05-2010
Publisher: Springer Science and Business Media LLC
Date: 1997
DOI: 10.1007/PL00000064
Abstract: The major histocompatibility complex (MHC) contains genes which confer susceptibility to numerous diseases and must be important in primate evolution. In some instances, genes have been mapped to the region between human histocompatibility leukocyte antigen (HLA)-B and tumor necrosis factor (TNF) but precise localization has proven difficult especially since this region is subject to insertions, deletions, and duplications. Utilizing computer similarity searches and coding prediction programs, we have identified several potential coding sequences between HLA-B and TNF. Three of these sequences, PERB11.2, PERB15, and PERB 18, are similar to members of multicopy gene families that are located in other regions of the MHC. The identification of numerous fragmented and intact retroelements (L1, Alu, LTR, and THE sequences) flanking the PERB11 and PERB15 genes suggests that these retroelements are involved in the duplication process. The evaluation of candidate genes for disease susceptibility within the MHC is complicated by their similarity to other members of multicopy gene families. The determination of sequence differences within and between species provides a strategy with which to investigate the candidate genes between HLA-B and TNF.
Publisher: Wiley
Date: 15-01-2023
DOI: 10.1111/TAN.14950
Abstract: Immune‐mediated necrotizing myopathy (IMNM) is a type of autoimmune myositis typically characterized clinically by proximal muscle weakness with elevated creatine kinase levels, pathologically by myofiber necrosis and regeneration with paucity of lymphocytic cell infiltration, and serologically by the presence of either of two myositis‐specific autoantibodies, anti‐SRP, and anti‐HMGCR antibodies. However, the HLA loci and alleles associated with IMNM are still not fully understood at least partly because IMNM was a relatively recently established condition. In this study, we genotyped the six HLA loci (HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1) in 250 patients (237 patients over age 18 years and 13 juvenile patients) diagnosed with IMNM based on clinicopathological features and autoantibody information and performed a case control study with Japanese healthy subjects. In the adult patients, specific HLA alleles associated with IMNM were identified at all HLA loci, with DRB1*08:03 showing the strongest association (OR = 2.5 p = 0.00000017). Furthermore, subgroup analysis with various clinical information showed that C*03:04 (OR = 3.7 p = 0.00012) was a higher risk allele for collagen disease in adult patients, and B*13:01 (OR = 23.2 p = 0.021) and C*03:04 (OR = 5.8 p = 0.0074) were higher risk for juvenile patients with anti‐HMGCR antibody‐positive IMNM. These findings will help to better understand the HLA genetic background and features of IMNM in designing future studies.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2016
Publisher: Wiley
Date: 03-1989
Abstract: DNA filter in situ hybridisation (FISH) was used to determine the presence of human papillomavirus (HPV) genotypes 6/11, 16/18, and 31/33 in cell scrapes of the cervix and vulva of 128 women who had precancerous lesions and/or HPV infection of the cervix diagnosed by cytology, colposcopy, and histology. HPV-DNA was found in 87 (68%) vulval and 95 (74%) cervical cell scrapes, and in both the vulval and cervical scrapes of 73 (57%) women, but not in either the vulva or the cervix of 19 women (15%). Of the HPV-DNA-positive smears, the prevalence of the HPV types was 61% HPV 16/18, 14% HPV 6/11, 3% HPV 31/33, and 22% HPV 6/11 and 16/18. By contrast, HPV-DNA was not detected in the cervical smears of a control group of 35 women who were assessed to be free of cervical abnormalities by colposcopy and cytology. The epithelial response of the vulva and the cervix to application of 5% acetic acid was assessed by colposcopy and the results correlated with the presence of HPV genotypes. A possible or definite disorder of the cervix and vulva was detected by colposcopy in 95 (74%) and 96 (75%) of the 128 cases, respectively. The colposcopic assessment of the vulva was inconclusive in ten cases (8%), and only eight women (6%) were found to be free of both a vulval and cervical disorder. This study shows subclinical papillomavirus infections of the vulva frequently coexist with HPV infections and precancerous lesions of the cervix.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 27-01-2006
Publisher: Wiley
Date: 30-11-2013
DOI: 10.1111/TAN.12258
Abstract: Super high-resolution single molecule sequence-based typing (SS-SBT) is a human leukocyte antigen (HLA) DNA typing method to the field 4 level of allelic resolution (formerly known as eight-digit typing) to efficiently detect new and null alleles without phase ambiguity by combination of long ranged polymerase chain reaction (PCR) lification and next-generation sequencing (NGS) technologies. We previously reported the development and application of the SS-SBT method for the eight classical HLA loci, A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1. In this article, we describe the development of the SS-SBT method for three DRB1 linked loci, DRB3, DRB4 and DRB5 (DRB3/4/5) and characterization of DRB1-DRB3/4/5 haplotype structures to the field 4 level. Locus specific PCR primers for DRB3/4/5 were designed to lify the gene regions from intron 1 to exon 6 [3' untranslated region (3'UTR)]. In total 20 DRB1 and 13 DRB3/4/5 allele sequences were determined by the SS-SBT to the field 4 level without phase ambiguity using 19 DR51, DR52 and DR53 positive genomic DNA s les obtained from Japanese. Moreover, 18 DRB1-DRB3/4/5 haplotypes were estimated to the field 4 level by the SS-SBT method in contrast to 10 haplotypes estimated by conventional methods to the field 1 level (formerly known as two digit typing). Therefore, DRB1-DRB3/4/5 haplotyping by SS-SBT is expected to provide informative data for improved HLA matching in medical research, transplantation procedures, HLA-related disease studies and human population ersity studies.
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-8546-3_8
Abstract: Super high resolution-single molecule-sequence-based typing (SS-SBT) is an HLA DNA typing method to the field 4 level of allelic resolution (formerly known as 8-digit typing) to efficiently detect novel and null alleles without phase ambiguity by combination of long ranged PCR lification and next-generation sequencing (NGS) technologies. In this chapter, we describe three basic steps, long ranged PCR, NGS, and allele assignment.
Publisher: InTech
Date: 19-03-2014
DOI: 10.5772/57556
Publisher: Wiley
Date: 12-2002
DOI: 10.1034/J.1600-065X.2002.19008.X
Abstract: The major histocompatibility complex (MHC) genomic region is composed of a group of linked genes involved functionally with the adaptive and innate immune systems. The class I and class II genes are intrinsic features of the MHC and have been found in all the jawed vertebrates studied so far. The MHC genomic regions of the human and the chicken (B locus) have been fully sequenced and mapped, and the mouse MHC sequence is almost finished. Information on the MHC genomic structures (size, complexity, genic and intergenic composition and organization, gene order and number) of other vertebrates is largely limited or nonexistent. Therefore, we are mapping, sequencing and analyzing the MHC genomic regions of different human haplotypes and at least eight nonhuman species. Here, we review our progress with these sequences and compare the human MHC structure with that of the nonhuman primates (chimpanzee and rhesus macaque), other mammals (pigs, mice and rats) and nonmammalian vertebrates such as birds (chicken and quail), bony fish (medaka, pufferfish and zebrafish) and cartilaginous fish (nurse shark). This comparison reveals a complex MHC structure for mammals and a relatively simpler design for nonmammalian animals with a hypothetical prototypic structure for the shark. In the mammalian MHC, there are two to five different class I duplication blocks embedded within a framework of conserved nonclass I and/or nonclass II genes. With a few exceptions, the class I framework genes are absent from the MHC of birds, bony fish and sharks. Comparative genomics of the MHC reveal a highly plastic region with major structural differences between the mammalian and nonmammalian vertebrates. Additional genomic data are needed on animals of the reptilia, crocodilia and marsupial classes to find the origins of the class I framework genes and ex les of structures that may be intermediate between the simple and complex MHC organizations of birds and mammals, respectively.
Publisher: Elsevier BV
Date: 06-1999
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.YGENO.2006.11.002
Abstract: The construction of a cynomolgus macaque (Macaca fascicularis, Mafa) BAC library for genomic comparison between rhesus and cynomolgus macaques is necessary to promote the cynomolgus macaque as one of the important experimental animals for future medical and biological research. In this paper, we constructed a cynomolgus macaque BAC library and a map of the MHC (Mafa) genomic region for comparison of the genomic organization and nucleotide similarities between the human, the chimpanzee, and the rhesus macaque. The BAC library consists of 221,184 clones with an average insert size of 83 kb, providing a sixfold coverage of the haploid genome. A total of 114 BAC clones and 54 PCR primer sets were used to construct a 4.3-Mb contig of the MHC region. Diversity analysis of genomic sequence from selected subregions of the MHC revealed that the cynomolgus sequence varied compared to rhesus macaque, human, and chimpanzee sequences by 0.48, 4.15, and 4.10%, respectively. From these findings, we conclude that the BAC library and Mafa genomic map are useful tools for genome analysis and will have important applications for comparative genomics and identifying regions of consequence in medical research.
Publisher: Springer Science and Business Media LLC
Date: 08-2004
DOI: 10.1007/S00335-004-2349-5
Abstract: hRDH-E2 is a member of the short-chain alcohol dehydrogenase/reductase (SDR) family that converts retinol to retinaldehyde as the first and rate-limiting step in the retinoic acid synthetic pathway. This pathway is critical for the maintenance of epidermal homeostasis in vivo. Previously, we reported that the mRNA levels of hRDH-E2 in psoriatic skin were elevated significantly compared with that in healthy in idual skin and psoriatic unaffected skin. The gene encoding hRDH-E2 is located on Chromosome 8 close to a candidate region for psoriasis and therefore is a functional and positional candidate for this disorder. In the present study, the transcription start sites for hRDH-E2 gene transcription in the lung were found to be more upstream of those that were identified previously in keratinocytes. Consequently, differences in the nucleotide sequence were determined for all of the coding exons, untranslated regions, and at least 2850 bp of 5'-noncoding sequence of hRDH-E2 by direct sequencing of polymerase chain reaction (PCR)- lified DNA s les obtained from 8 psoriatic patients and 8 healthy controls. One polymorphic microsatellite marker at the noncoding 3' end of the gene and six single nucleotide polymorphisms (SNPs) (three in the 5' flanking sequence, two in the coding sequence, and one in the intronic sequence) were identified. One of the SNPs was nonsynonymous in the second exon with an allelic variation between the amino acid sequences Arg and Trp. The microsatellite marker and the six SNPs were all genotyped in 100 Japanese psoriatic patients and 120 controls. However, there were no statistically significant differences in the genotype or allele frequency distributions between the cases and controls. On this basis, we conclude that the polymorphisms that we detected for the hRDH-E2 gene do not contribute to the etiology of psoriasis but may be important in diseases of other tissues.
Publisher: Wiley
Date: 25-04-2019
DOI: 10.1111/IJI.12426
Abstract: Polymorphic Alu insertions (POALINs) are found throughout the human genome and have been used in various studies to infer geographic origin of human populations. The main aim of this study was to determine the allele and haplotype frequencies of five POALINs, AluHF, AluHG, AluHJ, AluTF and AluMICB, within the major histocompatibility complex (MHC) class I region of 95 UAE Arabs, and correlate their frequencies to those of the HLA-A, HLA-C and HLA-B class I allele lineages. Evolutionary relationships between the POALINs of the Arabs and those previously studied in populations of African, Asian and European descent were compared. At each of the five Alu loci (AluHF, AluHG, AluHJ, AluTF and AluMICB), Alu insertion was designated as Alu(locus)*02 and absence was Alu(locus)*01. The AluHG insertion (AluHG*02) had the highest frequency (0.332), followed by AluHF*02 (0.300), AluHJ*02 (0.263), AluMICB*02 (0.111) and AluTF*02 (0.058). Of the 270 Alu-HLA haplotypes pairs in the UAE Arabs, 110 had no Alu insertion, and 54 had an Alu insertion at >50% per haplotype. An Alu insertion >75% per haplotype was found between AluMICB*02 and HLA-B*14, HLA-B*22, HLA-B*44, HLA-B*55, HLA-B*57 and HLA-B*73, and with HLA-C*01 and HLA-C*18 AluHJ*02 with HLA-A*01, HLA-A*19, HLA-A*24 and HLA-A*32 AluHG*02 with HLA-A*02 and HLA-B*18 and AluHF*02 with HLA-A*10. The genotyped allele and haplotype frequencies of the MHC POALINs in UAE Arabs were compared with the results of 30 previously published Asian, European, American and African populations. Phylogenetic and multidimensional scaling (MDS) analysis of the relative MHC POALINs allele and haplotype frequencies revealed that the UAE Arabs have a similar lineage to Caucasians and the most distant genetic relationship to the Waorani native American population of Ecuador. The structure of both the phylogenetic tree and the MDS analysis supports the Out of Africa theory of human evolution. The nature of the clusters suggests the Arabian Middle East represents a crossroads from which human populations migrated towards Asia in the east and Europe to the north-west.
Publisher: Wiley
Date: 05-2001
DOI: 10.1034/J.1399-0039.2001.057005397.X
Abstract: The human major histocompatibility complex (MHC) class III region spanning approximately 760 kb is characterized by a remarkably high gene density with 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loci to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loci. However, it has been difficult to precisely localize these susceptibility loci to a single gene due to a paucity to date of polymorphic markers in the HLA class III region. To facilitate disease mapping within this region, we have analyzed 2 approximately 5 bases short tandem repeats (microsatellites) in this region. A total of 297 microsatellites were identified from the genomic sequence, consisting of 69 di-, 62 tri-, 107 tetra-, and 59 penta-nucleotide repeats. It was noted that among them as many as 17 microsatellites were located within the coding sequence of expressed genes (NOTCH4, PBX2, RAGE, G16, LPAAT, PPT2, TNXB, P450-CYP21B, G9a, HSP70-2, HSP70-1, HSP-hom, MuTSH5 and BAT2). Eight microsatellite repeats were collected as polymorphic markers due to their high number of alleles (11.9 on average) as well as their high polymorphic content value (PIC) (0.63). By combining the 38 and the 22 polymorphic microsatellites we have previously collected in the HLA class I and class II regions, respectively, we have now established a total of 68 novel genetic markers which are uniformly interspersed with a high density of one every 63.3 kb throughout the HLA region. This collection of polymorphic microsatellites will enable us to search for the location of any disease susceptible loci within the HLA region by association analysis.
Publisher: Frontiers Media SA
Date: 18-01-2021
DOI: 10.3389/FGENE.2020.594318
Abstract: The genomic region (~4 Mb) of the human major histocompatibility complex (MHC) on chromosome 6p21 is a prime model for the study and understanding of conserved polymorphic sequences (CPSs) and structural ersity of ancestral haplotypes (AHs)/conserved extended haplotypes (CEHs). The aim of this study was to use a set of 95 MHC genomic sequences downloaded from a publicly available BioProject database at NCBI to identify and characterise polymorphic human leukocyte antigen (HLA) class I genes and pseudogenes, MICA and MICB , and retroelement indels as haplotypic lineage markers, and single-nucleotide polymorphism (SNP) crossover loci in DNA sequence alignments of different haplotypes across the Olfactory Receptor ( OR ) gene region (~1.2 Mb) and the MHC class I region (~1.8 Mb) from the GPX5 to the MICB gene. Our comparative sequence analyses confirmed the identity of 12 haplotypic retroelement markers and revealed that they partitioned the HLA-A/B/C haplotypes into distinct evolutionary lineages. Crossovers between SNP-poor and SNP-rich regions defined the sequence range of haplotype blocks, and many of these crossover junctions occurred within particular transposable elements, lncRNA, OR12D2, MUC21, MUC22, PSORS1A3, HLA-C, HLA-B , and MICA . In a comparison of more than 250 paired sequence alignments, at least 38 SNP-density crossover sites were mapped across various regions from GPX5 to MICB . In a homology comparison of 16 different haplotypes, seven CEH/AH ( 7.1, 8.1, 18.2, 51.x, 57.1, 62.x , and 62.1 ) had no detectable SNP-density crossover junctions and were SNP poor across the entire ~2.8 Mb of sequence alignments. Of the analyses between different recombinant haplotypes, more than half of them had SNP crossovers within 10 kb of LTR16B/ERV3-16A3_I, MLT1, Charlie , and/or THE1 sequences and were in close vicinity to structurally polymorphic Alu and SVA insertion sites. These studies demonstrate that (1) SNP-density crossovers are associated with putative ancestral recombination sites that are widely spread across the MHC class I genomic region from at least the telomeric OR12D2 gene to the centromeric MICB gene and (2) the genomic sequences of MHC homozygous cell lines are useful for analysing haplotype blocks, ancestral haplotypic landscapes and markers, CPSs, and SNP-density crossover junctions.
Publisher: The Endocrine Society
Date: 03-1981
Abstract: It has been previously reported that men with and without known disease can produce milk, but no studies to date have demonstrated that their secretion contains milk constituents produced specifically by the breast. The present study shows the presence of lactose, alpha-lactalbumin, and lactoferrin in the breast secretion of a 27-yr-old male who had galactorrhea associated with hyperprolactinaemia. The concentrations of lactose, proteins, and electrolytes in the breast secretion of this man are within the range of colostrum and milk obtained from normal lactating women.
Publisher: Springer Berlin Heidelberg
Date: 1997
Publisher: Wiley
Date: 09-2003
DOI: 10.1034/J.1399-0039.2003.00092.X
Abstract: A large proportion of Japanese with the HLA-B48 allele have a MICA gene deletion associated with a MICB null allele within the class I region of the Major Histocompatibility Complex (MHC). Here, we report for the first time a novel positive association between the presence of a polymorphic Alu insertion, AluyMICB, within the first intron of the MICB gene and the MICAdel/MICBnull/HLA-B48 haplotype for five of six well-characterized Japanese cell-lines. The AluyMICB insertion was found to be present at a frequency of 0.242 in 86 Japanese tissue donors and in four of the five in iduals with the HLA-B48 allele. The AluyMICB insertion was also associated with at least three different MICB alleles, *0102, *0107N and *0105, and three different HLA-B alleles, B13, B48 and B57, respectively, in the seven Workshop cell-lines (the 4th Asia-Oceania Histocompatibility Workshop, and the 10th International Histocompatibility Workshop) and the six Japanese cell-lines that were selected for this study. Based on the analysis of associations between different polymorphic markers within the beta block, the MICB*0102 allele was inferred to be the ancestral form of the MICB*0105 and MICB*0107N alleles. The AluyMICB polymorphism can now be used to further investigate its relationship with other MICB alleles and consequently their origins. In addition, we have examined the absence and presence of three other polymorphic Alu markers distributed within the alpha block of the class I region of the HLA-B48/AluyMICB haplotype. We conclude that the extended HLA-B haplotypes are best defined by considering multiple genomic sites including the four polymorphic Alu insertions described in this study.
Publisher: Wiley
Date: 08-2001
DOI: 10.1034/J.1399-0039.2001.580203.X
Abstract: MICA or PERB11.1 is a polymorphic major histocompatibility complex (MHC) class I-related gene located 46 kb centromeric of the HLA-B gene in the HLA class I region. It is expressed mainly in gut epithelial cells, keratinocytes, endothelial cells, fibroblasts and monocytes, and is upregulated by heat stress. MICA has been found to interact with gamma delta T cells, alpha beta CD8(+) and natural killer (NK) cells bearing the NKG2D/DAP10 receptor. The MICA gene displays a high degree of polymorphism with at least 54 alleles. In the present study, polymorphic exons 2, 3 and 4 of the MICA gene were analyzed using sequencing based typing (SBT) in 255 unrelated healthy northeastern Thais. Thirteen previously reported MICA alleles were detected. MICA*008, *010, *002 and *019 were highly predominant with the allele frequencies of 21.4%, 18.2%, 17.6% and 15.3%, respectively. Five of these 13 MICA alleles show significantly different frequencies from those of the Japanese and Caucasian populations. Interestingly, MICA052, which is a very rare allele in other populations, was prevalent with the allele frequency of 8.2%, mainly on the HLA haplotype carrying HLA-B*13 in this population. Strong linkage disequilibria were observed between MICA and HLA-B, as similarly observed in other populations, namely MICA*010-B*4601, MICA052-B*13, MICA*002-B*5801, and MICA*019-B*15 (1502, 1508, 1511, 1515, 1528, 1530). A large variety of three-locus (MICA - HLA-B - HLA-Cw) and six-locus (HLA-DQB1 - HLA-DRB1 - MICA - HLA-B - HLA-Cw - HLA-A) haplotypes were recognized in the northeastern Thai population. This is the first report on MICA allelic distribution in Southeast Asian populations. These data will provide the important basis for future analyses on the potential role of the MICA gene in disease susceptibility and transplantation matching in Southeast Asian populations.
Publisher: Wiley
Date: 02-07-2012
Publisher: Springer Science and Business Media LLC
Date: 12-2006
Abstract: The quail and chicken major histocompatibility complex ( Mhc ) genomic regions have a similar overall organization but differ markedly in that the quail has an expanded number of duplicated class I, class IIB, natural killer (NK)-receptor-like, lectin-like and BG genes. Therefore, the elucidation of genetic factors that contribute to the greater Mhc ersity in the quail would help to establish it as a model experimental animal in the investigation of avian Mhc associated diseases. The main aim here was to characterize the genetic and genomic features of the transcribed major quail MhcIIB ( CojaIIB ) region that is located between the Tapasin and BRD2 genes, and to compare our findings to the available information for the chicken MhcIIB ( BLB ). We used four approaches in the study of the quail MhcIIB region, (1) haplotype analyses with polymorphic loci, (2) cloning and sequencing of the RT-PCR CojaIIB products from in iduals with different haplotypes, (3) genomic sequencing of the CojaIIB region from the in iduals with the different haplotypes, and (4) phylogenetic and duplication analysis to explain the variability of the region between the quail and the chicken. Our results show that the Tapasin-BRD2 segment of the quail Mhc is highly variable in length and in gene transcription intensity and content. Haplotypic sequences were found to vary in length between 4 to 11 kb. Tapasin-BRD2 segments contain one or two major transcribed CojaIIBs that were probably generated by segmental duplications involving c-type lectin-like genes and NK receptor-like genes, gene fusions between two CojaIIBs and transpositions between the major and minor CojaIIB segments. The relative evolutionary speed for generating the MhcIIBs genomic structures from the ancestral BLB2 was estimated to be two times faster in the quail than in the chicken after their separation from a common ancestor. Four types of genomic rearrangement elements (GRE), composed of simple tandem repeats (STR), were identified in the MhcIIB genomic segment located between the Tapasin-BRD2 genes. The GREs have many more STR numbers in the quail than in the chicken that displays strong linkage disequilibrium. This study suggests that the Mhc classIIB region has a flexible genomic structure generated by rearrangement elements and rapid SNP accumulation probably as a consequence of the quail adapting to environmental conditions and pathogens during its migratory history after its ergence from the chicken.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/565296
Abstract: We investigated polymorphisms of the human leukocyte antigen (HLA) class I (A, B, and C) loci of a Han population ( n , 239) from the Yunnan province, Southwest China, using high-resolution polymerase chain reaction-Luminex (PCR-Luminex) typing. We combined the HLA data from this study with the KIR genotypes from a previous study of this Han population to analyze the combination of KIR/HLA ligands. A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population. The frequencies of A * 11:01, A * 24:02, B * 40:01, B * 46:01, C * 01:02, C * 03:04, and C * 07:02 were all 10%. The following haplotypes were common, with frequencies 5%: 1 A-B ( A * 02:07- B * 46:01), 2 A-C ( A * 02:07- C * 01:02, and A * 11:01- C * 07:02), 4 C-B ( B * 13:01- C * 03:04, B * 40:01- C * 07:02, B * 46:01- C * 01:02 and B * 58:01- C * 03:02), and 1 A-C-B ( A * 02:07- C * 01:02- B * 46:01). Analysis of KIR3D and their ligands HLA-A3/A11 and HLA-Bw4 showed that the frequencies of 3DL2 + -A3/A11 + and 3DL2 + -A3/A11 − were 0.527 and 0.473, and the frequencies of 3DL1 + -Bw4 + , 3DL1 + -Bw4 − , 3DL1 − -Bw4 + , and 3DL1 − -Bw4 − were 0.552, 0.397, 0.038, and 0.013, respectively. The results of KIR/HLA-C combination analysis showed that all in iduals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239), followed by two pairs (46/239), three pairs (33/239), and no pairs (3/239). Comparison of KIR gene and HLA gene and their pair frequency between Yunnan Han and the isolated Han (FYDH) who also lived in Yunnan province showed no significant difference ( P 0.05 ) in KIR frequencies, but significant differences ( P 0.05 ) for some HLA allele frequencies. In addition, there was no significant difference ( P 0.05 ) between the two populations for KIR/HLA pairs.
Publisher: Oxford University Press (OUP)
Date: 14-07-2004
Publisher: Springer Science and Business Media LLC
Date: 02-2002
DOI: 10.1007/S00251-001-0409-5
Abstract: We describe the finding of an Alu repeat dimorphism within the first intron of the MICB gene. The frequencies of the two AluyMICB alleles, AluyMICB*0(absence of insertion) and AluyMICB*1(presence of insertion), and their associations with the highly polymorphic HLA-B locus were determined for 51 human cell lines and for 109 and 200 Caucasians and northeastern Thais, respectively. Analysis of the AluyMICB and HLA-B allelic relationships revealed that AluyMICB*1 occurred at relatively low gene frequency (0.118-0.157) [corrected] but was strongly associated with HLA-B17 (HLA-B57,HLA-B58) and HLA-B13. The AluyMICB locus provides a useful dimorphic marker for investigations on the level of linkage disequilibrium between MICB, MICA, and HLA-B loci.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2005
DOI: 10.1007/S00251-005-0774-6
Abstract: The Major Histocompatibility Complex (Mhc) genomic region of many vertebrates is known to contain at least one highly polymorphic class II gene that is homologous in sequence to one or other of the human Mhc DRB1 class II genes. The ersity of the avian Mhc class II gene sequences have been extensively studied in chickens, quails, and some songbirds, but have been largely ignored in the oceanic birds, including the flightless penguins. We have previously reported that several penguin species have a high degree of polymorphism on exon 2 of the Mhc class II DRB1-like gene. In this study, we present for the first time the complete nucleotide sequences of exon 2, intron 2, and exon 3 of the DRB1-like gene of 20 Humboldt penguins, a species that is presently vulnerable to the dangers of extinction. The Humboldt DRB1-like nucleotide and amino acid sequences reveal at least eight unique alleles. Phylogenetic analysis of all the available avian DRB-like sequences showed that, of five penguin species and nine other bird species, the sequences of the Humboldt penguins grouped most closely to the Little penguin and the mallard, respectively. The present analysis confirms that the sequence variations of the Mhc class II gene, DRB1, are useful for discriminating among in iduals within the same penguin population as well those within different penguin population groups and species.
Publisher: International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA)
Date: 2014
Abstract: CD117 is a cytokine receptor expressed on the surface of hematopoietic stem cells with a likely role in cell survival, proliferation and differentiation. In order to study the differentiation activity of porcine CD117 hematopoietic cells in vitro and in vivo we prepared an anti-swine CD117 Mab (2A1) with high specificity for flow-cytometrical analysis. The 2A1 Mab did not recognize mouse or human mast cells suggesting that 2A1 is species-specific. Swine bone marrow (BM) CD117+ cells differentiated in vitro mainly into erythroid and monocyte lineages in the methylcellulose-based colony assay. When the swine BM CD117+ cells were transplanted in vivo into immunodeficient NOG (NOD/SCID/IL-2gc-null) mice, a significant amount of swine CD45+ leukocytes, including CD3 positive T cells, were developed in the mice. These results revealed that the swine BM CD117+ cells possess hematopoietic stem rogenitor activity and when monitored in immunodeficient mice or in vitro they can develop into lymphoid, erythroid, and myeloid cells efficiently with the new monoclonal antibody.
Publisher: Wiley
Date: 04-08-2012
DOI: 10.1111/J.1399-0039.2012.01941.X
Abstract: Current human leukocyte antigen (HLA) DNA typing methods such as the sequence-based typing (SBT) and sequence-specific oligonucleotide (SSO) methods generally yield ambiguous typing results because of oligonucleotide probe design limitations or phase ambiguity for HLA allele assignment. Here we describe the development and application of the super high-resolution single-molecule sequence-based typing (SS-SBT) of HLA loci at the 8-digit level using next generation sequencing (NGS). NGS which can determine an HLA allele sequence derived from a single DNA molecule is expected to solve the phase ambiguity problem. Eight classical HLA loci-specific polymerase chain reaction (PCR) primers were designed to lify the entire gene sequences from the enhancer-promoter region to the 3' untranslated region. Phase ambiguities of HLA-A, -B, -C, -DRB1 and -DQB1 were completely resolved and unequivocally assigned without ambiguity to single HLA alleles. Therefore, the SS-SBT method described here is a superior and effective HLA DNA typing method to efficiently detect new HLA alleles and null alleles without ambiguity.
Publisher: Elsevier BV
Date: 04-1998
Abstract: Mouse monoclonal antibodies (mAbs) were raised against the major capsid protein, L1, of human papillomavirus type 16 (HPV16), produced in Escherichia coli with the expression plasmid pTrcL1. Epitope specificity could be assigned to 11 of these 12 antibodies using a series of linear peptides and fusion proteins from HPV16. One mAb (MC53) recognized a novel linear epitope that appears to be unique to the HPV16 genotype. A further 11 mAbs were characterized as recognizing novel and previously defined linear and conformational epitopes shared among more than one HPV genotype. The apparently genotype specific mAb could be useful for the development of diagnostic tests for vegetative virus infection in clinical specimens.
Publisher: Wiley
Date: 18-02-2014
DOI: 10.1002/TOX.21839
Abstract: Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP-induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty-eight SNP markers within the PNPLA6 gene were tested for association in a case-control study of 188 affected in iduals and 401 age-matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS.
Publisher: Wiley
Date: 15-08-2005
DOI: 10.1111/J.1399-0039.2005.00457.X
Abstract: Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2013
DOI: 10.1007/S00251-013-0721-X
Abstract: Psoriasis is a common human skin disease whereby abnormal production of inflammatory mediators is believed to play an important role in its pathogenesis. The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12 and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23, were identified as psoriasis-susceptibility genetic factors in recent candidate gene and genome-wide association studies of Chinese and Europeans. Since there are significant differences in the incidence of psoriasis between Europeans and Japanese suggesting a genetic ethnic effect, we examined the association of IL12B and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560 controls and compared our results with those previously published for Europeans and Asians. Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR) = 1.35, P = 4.94E-04) and rs6887695 (OR = 1.32, P = 2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was found for the IL12B gene protective haplotype C-C (OR = 0.71, P = 1.84E-04) in Japanese, as previously elucidated in the studies of European ancestry.
Publisher: Frontiers Media SA
Date: 29-05-2020
Publisher: Wiley
Date: 03-2003
DOI: 10.1034/J.1399-0039.2003.00007.X
Abstract: The major histocompatibility complex (MHC) is known to have a role in the development of non-melanoma skin cancer (NMSC), although the genes and mechanisms involved have yet to be determined. To identify the susceptibility locus for NMSC within the MHC, we used a collection of well-defined polymorphic microsatellite markers from the Human leucocyte antigen (HLA) region for an association analysis of 150 cases with NMSC and 200 healthy controls selected from the Busselton population in Western Australia. High-resolution mapping was undertaken using a total of 40 highly polymorphic markers located at regular intervals across the HLA region (3.6Mb). Polymerase chain reaction (PCR) analysis was initially performed on pooled DNA markers to detect those markers that showed different allele profiles. Statistically significant differences in allelic frequencies (differentiating alleles) were found between cases and controls at three polymorphic microsatellite loci within a 470-kb genomic susceptibility region ranging between 6 kb centromeric of the HLA-B gene and intron 5 of the DDR gene. Interestingly, this genome region corresponded completely with the psoriasis-susceptibility locus. The three differentiating alleles and another four markers outside the susceptibility region were then PCR tested by in idual genotyping of cases and controls. The newly identified susceptibility locus for NMSC within the MHC was found to be significantly different between the cases and controls by comparisons of allele frequencies at the three differentiating loci estimated from DNA pools and then confirmed by in idual genotyping. This is the first study using high density microsatellite markers to localize a NMSC susceptibility region within the human genome.
Publisher: Bioscientifica
Date: 09-1977
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/J.GENE.2003.09.014
Abstract: We have identified a novel human gene designated as IDH3GL (isocitrate dehydrogenase 3 gamma-like) that is expressed specifically in human testis. The gene corresponds in sequence to an EST (expressed sequence tag) A1476435 that was first detected by differential expression analysis using a microarray assay. The full-length cDNA sequence (1037 bp) was isolated from the human testis 5'-3'-RACE cDNA libraries and found to have 83% nucleotide sequence identity with part of the IDH3G (isocitrate dehydrogenase 3 gamma). The IDH3GL gene consists of 3 exons spanning approximately 220 kb within the region of the NELL1 gene on chromosome 11p15.1. Sequence analysis of the IDH3GL cDNA revealed the presence of a premature stop codon at nucleotide positions 337-339 that results in a truncated peptide with 112 amino acids. This stop codon is conserved in various human ethnic populations and in the chimpanzee (Pan troglodytes). In order to assess the functional status of IDH3GL, especially in relation to the presence of the putative premature stop codon, single nucleotide polymorphisms (SNPs) were screened in the upstream, coding and non-coding regions of the IDH3GL gene in a Japanese population. As a result, a total of 10 SNPs were identified, seven were novel and one of them was a non-synonymous amino acid substitution from Leu to Val. We conclude that the IDH3GL gene sequence is a splice variant of the NELL1 gene and that it probably evolved from a transposed pseudogene of the IDH3 gene.
Publisher: Wiley
Date: 03-2010
DOI: 10.1111/J.1399-0039.2010.01465.X
Abstract: We investigated polymorphic Alu insertion (POALIN) frequencies at five loci in the major histocompatibility complex (MHC) class II genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-DRB1 and -DQB1 genes for 100 Japanese, 174 Australian Caucasians and 67 HLA reference cell lines obtained from different ethnic groups. The POALINs varied in frequency between 11% and 57% with significant differences between the Japanese and Caucasians at three loci. One POALIN locus deviated significantly from Hardy-Weinberg equilibrium (HWE) and four POALIN loci were in significant linkage disequilibrium and had a high percentage association with a variety of HLA-DRB1 or -DQB1 two-digit alleles. Inferred haplotype analysis among two-locus, five-locus and seven-locus haplotype structures showed maximum differences between the Japanese and Caucasians with the seven-locus haplotypes. The most common multilocus haplotype in Caucasians was DRB1*1501/DQB1*0602/AluDQ1/AluDRB1/AluORF10/AluDPB2 (6.7%), whereas the second most common allele HLA-DRB1*15 (17.5%) in Japanese was associated with three or four Alu insertions. The HLA class II POALINs also differentiated within and between HLA-DRB1 super-haplotypes DR1, DR8, DR51, DR52 and DR53. This is the first comparative population study of multilocus POALINs in the HLA class II region, which shows that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic markers for the identification of allele and haplotype lineages and variations within the same and/or different populations.
Publisher: Springer Science and Business Media LLC
Date: 20-09-2011
DOI: 10.1007/S00251-011-0572-2
Abstract: The swine is an important animal model for allo- and xeno-transplantation donor studies, which necessitates an extensive characterization of the expression and sequence variations within the highly polygenic and polymorphic swine leukocyte antigen (SLA) region. Massively parallel pyrosequencing is potentially an effective new 2ndGen method for simultaneous high-throughput genotyping and detection of SLA class I gene expression levels. In this study, we compared the 2ndGen method using the Roche Genome Sequencer 454 FLX with the conventional method using sub-cloning and Sanger sequencing to genotype SLA class I genes in five pigs of the Clawn breed and four pigs of the Landrace breed. We obtained an average of 10.4 SLA class I sequences per pig by the 2ndGen method, consistent with the inheritance data, and an average of only 6.0 sequences by the conventional method. We also performed a correlation analysis between the sequence read numbers obtained by the 2ndGen method and the relative expression values obtained by quantitative real-time PCR analysis at the allele level. A significant correlation coefficient (r = 0.899, P < 0.01) was observed between the sequence read numbers and the relative quantitative values for the expressed classical SLA class I genes SLA-1, SLA-2, and SLA-3, suggesting that the sequence read numbers closely reflect the gene expression levels in white blood cells. Overall, five novel class I sequences, different haplotype-specific expression patterns and a splice variant for one of the SLA class I genes were identified by the 2ndGen method at greater efficiency and sensitivity than the conventional method.
Publisher: Elsevier BV
Date: 09-1986
DOI: 10.1016/S0140-6736(86)90187-X
Abstract: 200 years have now passed since Darwin was born and scientists around the world are celebrating this important anniversary of the birth of an evolutionary visionary. However, the theories of his colleague Lamarck are treated with considerably less acclaim. These theories centre on the tendency for complexity to increase in organisms over time and the direct transmission of phenotypic traits from parents to offspring. Lamarckian concepts, long thought of no relevance to modern evolutionary theory, are enjoying a quiet resurgence with the increasing complexity of epigenetic theories of inheritance. There is evidence that epigenetic alterations, including DNA methylation and histone modifications, are transmitted transgenerationally, thus providing a potential mechanism for environmental influences to be passed from parents to offspring: Lamarckian evolution. Furthermore, evidence is accumulating that epigenetics plays an important role in many common medical conditions. Epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution. Further efforts should be exerted on studying the mechanisms by which this occurs so that public health measures can be undertaken to reverse or prevent epigenetic changes important in disease susceptibility. Perhaps in 2059 we will be celebrating the anniversary of both Darwin and Lamarck.
Publisher: Springer Science and Business Media LLC
Date: 12-2005
DOI: 10.1007/S00251-005-0053-6
Abstract: Continuous genomic sequence has been previously determined for the swine leukocyte antigen (SLA) class I region from the TNF gene cluster at the border between the major histocompatibility complex (MHC) class III and class I regions to the UBD gene at the telomeric end of the classical class I gene cluster (SLA-1 to SLA-5, SLA-9, SLA-11). To complete the genomic sequence of the entire SLA class I genomic region, we have analyzed the genomic sequences of two BAC clones carrying a continuous 237,633-bp-long segment spanning from the TRIM15 gene to the UBD gene located on the telomeric side of the classical SLA class I gene cluster. Fifteen non-class I genes, including the zinc finger and the tripartite motif (TRIM) ring-finger-related family genes and olfactory receptor genes, were identified in the 238-kilobase (kb) segment, and their location in the segment was similar to their apparent human homologs. In contrast, a human segment (alpha block) spanning about 375 kb from the gene ETF1P1 and from the HLA-J to HLA-F genes was absent from the 238-kb swine segment. We conclude that the gene organization of the MHC non-class I genes located in the telomeric side of the classical SLA class I gene cluster is remarkably similar between the swine and the human segments, although the swine lacks a 375-kb segment corresponding to the human alpha block.
Publisher: Wiley
Date: 02-2003
Publisher: Elsevier BV
Date: 2007
Publisher: Inderscience Publishers
Date: 2014
Publisher: Wiley
Date: 05-2006
DOI: 10.1111/J.1399-0039.2006.00586.X
Abstract: The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602 Pc = 0.130, OR = 4.3, B*3901 Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.
Publisher: MDPI AG
Date: 20-05-2019
DOI: 10.3390/CELLS8050480
Abstract: The HCP5 RNA gene (NCBI ID: 10866) is located centromeric of the HLA-B gene and between the MICA and MICB genes within the major histocompatibility complex (MHC) class I region. It is a human species-specific gene that codes for a long noncoding RNA (lncRNA), composed mostly of an ancient ancestral endogenous antisense 3′ long terminal repeat (LTR, and part of the internal pol antisense sequence of endogenous retrovirus (ERV) type 16 linked to a human leukocyte antigen (HLA) class I promoter and leader sequence at the 5′-end. Since its discovery in 1993, many disease association and gene expression studies have shown that HCP5 is a regulatory lncRNA involved in adaptive and innate immune responses and associated with the promotion of some autoimmune diseases and cancers. The gene sequence acts as a genomic anchor point for binding transcription factors, enhancers, and chromatin remodeling enzymes in the regulation of transcription and chromatin folding. The HCP5 antisense retroviral transcript also interacts with regulatory microRNA and immune and cellular checkpoints in cancers suggesting its potential as a drug target for novel antitumor therapeutics.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2015
Publisher: Wiley
Date: 08-1981
DOI: 10.1038/ICB.1981.34
Publisher: Wiley
Date: 06-07-2006
DOI: 10.1111/J.1399-0039.2006.00631.X
Abstract: A non-melanoma skin cancer (NMSC) susceptibility locus within the major histocompatibility complex (MHC) class I region was previously identified telomeric of the HLA-C gene using high-density microsatellite markers. Here, we have extended the previous microsatellite study by using the same DNA s les obtained from 154 NMSC patients and 213 normal controls from the town of Busselton in Western Australia and examined the relationship between five polymorphic Alu insertions (POALINs) within the MHC class I region and their association with NMSC. The genotype distribution of the AluyTF insertion that is located within the NMSC susceptibility region telomeric of the HLA-C gene was significantly increased according to the Fisher's exact test in the NMSC patients, and it was not in Hardy-Weinberg equilibrium in the control group. There was no difference between the cancer patients and controls for the genotypes of the AluyMICB locus within intron 1 of the MICB gene and the other three POALINs (AluyHJ, AluyHG and AluyHF) that are located within the genomic region of the HLA-A, -G and -F gene cluster. The test for significant linkage disequilibrium for 10 pairs of POALIN loci and estimations of two locus POALIN haplotype frequencies also revealed AluyTF differences between the cases and controls. In conclusion, the MHC class I POALIN, AluyTF, that is located within the NMSC susceptibility locus and near the HLA-C gene was strongly associated with NMSC. This finding, using five different polymorphic Alu insertion markers, supports the previous microsatellite association study that one or more genes located in close proximity to the AluyTF insertion has a potential role in NMSC.
Publisher: Wiley
Date: 06-04-2022
DOI: 10.1111/TAN.14611
Abstract: HLA sequence‐based DNA typing (SBT) by long‐range PCR lification (LR PCR) and next‐generation sequencing (NGS) is a high‐throughput DNA sequencing method (LR‐NGS‐SBT) for the efficient and sensitive detection of novel and null HLA alleles to the field‐4 level of allelic resolution without phase ambiguity. However, the accuracy and reliability of the HLA typing results using buccal cells (BCs) and saliva as genetic source materials for the LR‐NGS‐SBT method are dependent largely on the quality of the extracted genomic DNA (gDNA) because a large degree of gDNA fragmentation can result in insufficient PCR lification with the incorrect assignment of HLA alleles because of allele dropouts. In this study, we developed a new cost‐efficient swab storage gel (SSG) for wet swab collection of BCs (BC‐SSG) and evaluated its usefulness by performing different DNA analytical parameters including LR‐NGS‐SBT to compare the quality and quantity of gDNA extracted from BCs (in SSG or air dried), blood and saliva of 30 subjects. The BC‐SSG s les after 5 days of storage revealed qualitative and quantitative DNA values equivalent to that of blood and/or saliva and better than swabs that were only air‐dried (BC‐nSSG). Moreover, all the gDNA extracted from blood, saliva and BC‐SSG s les were HLA‐typed successfully to an equivalent total of 408 alleles for each s le type. Therefore, the application of BC‐SSG collection media for LR‐NGS‐SBT has benefits over BC dried s les (dry swabs) such as reducing retesting and the number of untestable BC s les because of insufficient DNA lification.
Publisher: Springer Science and Business Media LLC
Date: 10-2001
Publisher: Springer US
Date: 1994
Publisher: Wiley
Date: 02-2006
DOI: 10.1111/J.1348-0421.2006.TB03774.X
Abstract: Human CD93, also known as complement protein 1, q subcomponent, receptor (C1qRp), is selectively expressed by cells with a myeloid lineage, endothelial cells, platelets, and microglia and was originally reported to be involved in the complement protein 1, q subcomponent (C1q)-mediated enhancement of phagocytosis. The intracellular molecular events responsible for the regulation of its expression on the cell surface, however, have not been determined. In this study, the effect of protein kinases in the regulation of CD93 expression on the cell surface of a human monocyte-like cell line (U937), a human NK-like cell line (KHYG-1), and a human umbilical vein endothelial cell line (HUV-EC-C) was investigated using four types of protein kinase inhibitors, the classical protein kinase C (cPKC) inhibitor Go6976, the novel PKC (nPKC) inhibitor Rottlerin, the protein kinase A (PKA) inhibitor H-89 and the protein tyrosine kinase (PTK) inhibitor herbimycin A at their optimum concentrations for 24 hr. CD93 expression was analyzed using flow cytometry and glutaraldehyde-fixed cellular enzyme-linked immunoassay (EIA) techniques utilizing a CD93 monoclonal antibody (mAb), mNI-11, that was originally established in our laboratory as a CD93 detection probe. The nPKC inhibitor Rottlerin strongly down-regulated CD93 expression on the U937 cells in a dose-dependent manner, whereas the other inhibitors had little or no effect. CD93 expression was down-regulated by Go6976, but not by Rottlerin, in the KHYG-1 cells and by both Rottlerin and Go6976 in the HUV-EC-C cells. The PKC stimulator, phorbol myristate acetate (PMA), strongly up-regulated CD93 expression on the cell surface of all three cell-lines and induced interleukin-8 (IL-8) production by the U937 cells and interferon-gamma (IFN-gamma) production by the KHYG-1 cells. In addition, both Go6976 and Rottlerin inhibited the up-regulation of CD93 expression induced by PMA and IL-8 or IFN-gamma production in the respective cell-lines. Whereas recombinant tumor necrosis factor-alpha (rTNF-alpha) slightly up-regulated CD93 expression on the U937 cells, recombinant interleukin-1beta (rIL-1beta), recombinant interleukin-2 (rIL-2), recombinant interferon-gamma (rIFN-gamma) and lipopolysaccharide (LPS) had no effect. Taken together, these findings indicate that the regulation of CD93 expression on these cells involves the PKC isoenzymes.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2010
DOI: 10.1007/S10142-010-0168-1
Abstract: A small percentage (3%) of the 1.3 million copies of Alu sequences in the human genome is expressed in idually or as part of various gene transcripts with potential regulatory and pathophysiological importance. In order to better understand the role of repetitive elements within transcripts, this review focuses on Alu-containing transcripts of normal and cancerous tissue in a transcriptome-wide survey of the H-Invitational human transcript database on 106,825 tissue-derived transcripts expressed at 29,979 loci. The Alu elements in transcripts of cancerous tissues are significantly underrepresented in comparison to those in normal tissues. In this review, we propose a model for Alu-mediated siRNA down-regulation of Alu-containing transcripts in cancer tissues. In cancer or other rapidly iding tissues, hypomethylation of repeat element regions triggers the expression of transposon elements including Alu, which can potentially form double-stranded RNA molecules for use as templates to generate Alu-derived siRNAs (Alu-siRNAs). The generated Alu-siRNAs target endogenous messenger RNAs harbouring sequence similarity to Alu elements. This model correlates with the observation that there is substantial under-representation of Alu-containing mRNAs in cancer cells. This new perspective of gene regulation in disease conditions can provide a basis for starting to account for changes in complex gene network in cancer.
Publisher: Springer Science and Business Media LLC
Date: 03-1985
DOI: 10.1007/BF01310960
Publisher: Springer Science and Business Media LLC
Date: 08-2004
Publisher: Wiley
Date: 19-04-2005
DOI: 10.1046/J.1529-8817.2005.00183.X
Abstract: Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the in idual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and -B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA-B*57, AluyHJ and HLA-A*24 and HLA-A*01, and AluyHG and HLA-A*02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA-A and -B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese.
Publisher: Georg Thieme Verlag KG
Date: 08-1982
Publisher: Springer Science and Business Media LLC
Date: 11-2007
Abstract: Accurate analysis of DNA sequence variation in not only humans and animals but also other organisms has played a significant role in expanding our knowledge about genetic variety and ersity in a number of different biological areas. The search for an understanding of the causes of genetic variants and mutations has resulted in the development of a simple laboratory technique, known as the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, for the detection of single nucleotide polymorphisms (SNPs). PCR-RFLP allows rapid detection of point mutations after the genomic sequences are lified by PCR. The mutation is discriminated by digestion with specific restriction endonucleases and is identified by gel electrophoresis after staining with ethidium bromide (EtBr). This convenient and simple method is inexpensive and accurate for SNP genotyping and especially useful in small basic research studies of complex genetic diseases. The whole protocol takes only a day to carry out.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.ETAP.2009.11.007
Abstract: Sick building syndrome (SBS) is a chronic disorder caused by exposure to erse indoor environmental or chemical pollutants. This study examined the association between seven detoxification genes (CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTP1, and NAT2) and SBS in the Japanese population. One hundred eighty patients with SBS and 401 healthy controls were enrolled in this study. We examined the prevalence for total of eleven genetic polymorphisms of detoxification genes. However, no statistically significant differences in allele and genotype frequency distributions of eleven genetic polymorphisms of these detoxification genes were found between patients and controls. On this basis, we conclude that the polymorphisms that we assessed for the detoxification genes do not contribute to the etiology of SBS.
Publisher: Wiley
Date: 02-1981
DOI: 10.1038/ICB.1981.6
Abstract: Studies were undertaken to determine the progressive changes and relationships between the major constituents in the mammary secretion of breast feeding and non-breast feeding women during the initiation of lactation. The concentration of metabolites (lactose, glucose and urea), electrolytes and proteins (total protein, alpha-lactalbumin, lactoferrin, albumin, IgA, IgG and IgM) were measured in small s les of mammary secretion (0 . 5-5 . 0 ml). Colostrum during late pregnancy contained higher concentrations of proteins and lower concentrations of metabolites than milk in established lactation. Of the electrolytes, the concentrations of sodium, chloride and magnesium were higher, whereas potassium and calcium were lower in colostrum than in milk. The osmolality of the secretion remained relatively constant over the pre-partum and post-partum period. These findings showed that the initiation of lactation developed in two phases, first a limited secretion of milk constituents in late pregnancy and then true induction of lactation (lactogenesis) 32-40 h after delivery. The changes in the mammary secretion of non-breast feeding women during the first 3 days post-partum were similar to those observed in breast feeding women but reversed abruptly during the next 6 days, indicating the onset of mammary involution. This finding demonstrated that breast feeding is not a major factor for the initiation of lactation but is essential for the continuation of full lactation.
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1038/JHG.2008.5
Abstract: The human leukocyte antigen (HLA) super-locus is a genomic region in the chromosomal position 6p21 that encodes the six classical transplantation HLA genes and at least 132 protein coding genes that have important roles in the regulation of the immune system as well as some other fundamental molecular and cellular processes. This small segment of the human genome has been associated with more than 100 different diseases, including common diseases, such as diabetes, rheumatoid arthritis, psoriasis, asthma and various other autoimmune disorders. The first complete and continuous HLA 3.6 Mb genomic sequence was reported in 1999 with the annotation of 224 gene loci, including coding and non-coding genes that were reviewed extensively in 2004. In this review, we present (1) an updated list of all the HLA gene symbols, gene names, expression status, Online Mendelian Inheritance in Man (OMIM) numbers, including new genes, and latest changes to gene names and symbols, (2) a regional analysis of the extended class I, class I, class III, class II and extended class II subregions, (3) a summary of the interspersed repeats (retrotransposons and transposons), (4) ex les of the sequence ersity between different HLA haplotypes, (5) intra- and extra-HLA gene interactions and (6) some of the HLA gene expression profiles and HLA genes associated with autoimmune and infectious diseases. Overall, the degrees and types of HLA super-locus coordinated gene expression profiles and gene variations have yet to be fully elucidated, integrated and defined for the processes involved with normal cellular and tissue physiology, inflammatory and immune responses, and autoimmune and infectious diseases.
Publisher: Japanese Society of Veterinary Science
Date: 2008
DOI: 10.1292/JVMS.70.711
Abstract: We applied previously published PCR primer pairs to lify alleles at three polymorphic microsatellite loci to determine the genetic relationship of 6 bottlenose dolphins (Tursiops truncatus) that were living together in a Japanese aquarium. The three microsatellite loci were sufficient to determine the haplotype relationships of the six dolphins, which represented three different generations. It was confirmed that this genotyping method is simple and economical for assessing, establishing and maintaining genetic ersity in captive populations and will become a very effective technique for ex situ conservation in aquariums and zoos.
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Wiley
Date: 16-11-2004
DOI: 10.1111/J.1399-0039.2004.00327.X
Abstract: The human major histocompatibility (MHC) genomic region at chromosomal position 6p21 encodes the six classical transplantation HLA genes and many other genes that have important roles in the regulation of the immune system as well as in some fundamental cellular processes. This small segment of the human genome has been associated with more than 100 diseases, including common diseases--such as diabetes, rheumatoid arthritis, psoriasis, asthma and various autoimmune disorders. The MHC 3.6 Mb genomic sequence was first reported in 1999 with the annotation of 224 gene loci. The locus and allelic information of the MHC continue to be updated by identifying newly mapped expressed genes and pseudogenes based on comparative genomics, SNP analysis and cDNA projects. Since 1999, new innovations in bioinformatics and gene-specific functional databases and studies on the MHC genes have resulted in numerous changes to gene names and better ways to update and link the MHC gene symbols, names and sequences together with function, variation and disease associations. In this study, we present a brief overview of the MHC genomic structure and the recent information that we have gathered on the MHC gene loci via LocusLink at the National Centre for Biological Information () and the MHC genes' association with various diseases taken from publications and records in public databases, such as the Online Mendelian Inheritance in Man and the Genetic Association Database.
Publisher: Wiley
Date: 03-2000
DOI: 10.1002/(SICI)1522-2683(20000301)21:5<896::AID-ELPS896>3.0.CO;2-1
Publisher: Wiley
Date: 04-1999
Publisher: Springer Science and Business Media LLC
Date: 17-06-2008
DOI: 10.1007/S00251-008-0289-Z
Abstract: Our aim was to investigate microsatellite (MS) ersity and find crossover regions at 42 polymorphic MS loci in the swine leukocyte antigen (SLA) genomic region of 72 pigs with different well-defined homozygous and heterozygous SLA haplotypes. We analyzed the genetic polymorphisms of 42 MS markers in 23 SLA homozygous-heterozygous, common pig breeds with 12 SLA serological haplotypes and 49 National Institutes of Health (NIH) and Clawn homozygous-heterozygous miniature pigs with nine SLA serological or genotyped haplotypes including four recombinant haplotypes. In comparing the same and different haplotypes, both haplospecific patterns and allelic variations were observed at the MS loci. Some of the shared haplotype blocks extended over 2 Mb suggesting the existence of strong linkage disequilibrium (LD) in the entire SLA region. Crossover regions were easily defined by the MS markers within the class I and/or III region in the NIH and Clawn recombinant haplotypes. The present haplotype comparison shows that our set of MS markers provides a fast and cost-efficient alternative, or complementary, method to the serological or sequence-based determination of the SLA alleles for the characterization of SLA haplotypes and/or the crossover regions between different haplotypes.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2015
DOI: 10.1007/S00251-015-0867-9
Abstract: Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.
Publisher: Wiley
Date: 25-10-2006
DOI: 10.1002/AJMG.B.30443
Abstract: Many studies suggest that mitochondrial dysfunction is involved in the pathophysiology of schizophrenia. We performed a case-control study using tag SNPs in the mitochondrial uncoupling protein genes, UCP2, UCP4, and BMCP1/UCP5, to investigate their association with schizophrenia. These neuronal UCPs are expressed in various brain tissues and may exert a neuroprotective effect against increased oxidative stress. We found modest associations between schizophrenia and the four tag SNPs, rs660339 (odds ratio (OR) = 1.330 P = 0.0043) and rs649446 (OR = 0.739 P = 0.0069) in UCP2, and rs10807344 (OR = 0.622 P = 0.0029) and rs2270450 (OR = 0.704 P = 0.0043) in UCP4, all of which were statistically significant even after correcting for multiple comparisons. Moreover, we found a statistically significant synergistic interaction between UCP2 and UCP4 by using the multifactor dimensionality reduction (MDR) method. The synergistic interaction was also confirmed by the logistic regression analysis, where the maximal OR was obtained when the risk alleles at rs660339 and rs10807344 were simultaneously homozygous. In iduals possessing homozygous risk alleles at these two loci have a 7.6-fold risk of developing schizophrenia compared with those of minimal OR. Our findings suggest that UCP2 and UCP4 have a modest but important involvement in the genetic etiology of schizophrenia. This is the first report of the association between schizophrenia and neuronal UCPs.
Location: United States of America
No related grants have been discovered for jerzy kulski.