David Adelson

Sheep endogenous betaretroviruses (enJSRVs) and the hyaluronidase 2 (HYAL2) receptor in the ovine uterus and conceptus

Publisher: Oxford University Press (OUP)

Date: 08-2005

DOI: 10.1095/BIOLREPROD.105.039776

Abstract: The ovine genome contains approximately 20 copies of endogenous betaretroviruses (enJSRVs) that are highly related to two exogenous oncogenic viruses, Jaagsiekte sheep retrovirus (JSRV) and Enzootic nasal tumor virus. The cellular receptor for both JSRV and the enJSRVs is hyaluronidase 2 (HYAL2). In this study, we assessed expression of enJSRVs envelope (env) and HYAL2 mRNAs in the ovine uterus and conceptus (embryo/fetus and extraembryonic membranes) throughout gestation. By reverse transcription-polymerase chain reaction analyses, enJSRVs env were found to be expressed beginning in the Day 12 conceptus, whereas HYAL2 was expressed from Day 16. HYAL2 mRNA was detected throughout gestation in the placentome but not in the endometrium, whereas enJSRVs env expression was detected throughout gestation in endometrium and placentomes. The enJSRVs env mRNA was specifically expressed in the endometrial lumenal epithelium (LE) and glandular epithelium (GE) as well as the trophoblast giant binucleate cells (BNC) and multinucleated syncytia of the placenta. HYAL2 mRNA was only detected in the BNC and multinucleated syncytial plaques of the placentome. Partial sequencing of the transcriptionally active enJSRVs from sheep endometrium, placentomes, and placenta revealed expression of many enJSRV loci. Cloning of the expressed enJSRVs env mRNA from ovine uteroplacental tissues found sequences similar to the previously identified enJS5F16 and enJS56A1 gene with an intact open reading frame, although the polypeptides they encode were not studied. Collectively, results provide further support for our hypothesis that the enJSRVs Env have been beneficial to the host and are involved in protection of the uterus from viral infection and regulators of placental morphogenesis and function.

Interspersed repeats in the horse (Equus caballus); Spatial correlations highlight conserved chromosomal domains

Publisher: Wiley

Date: 10-11-2010

DOI: 10.1111/J.1365-2052.2010.02115.X

Abstract: The interspersed repeat content of mammalian genomes has been best characterized in human, mouse and cow. In this study, we carried out de novo identification of repeated elements in the equine genome and identified previously unknown elements present at low copy number. The equine genome contains typical eutherian mammal repeats, but also has a significant number of hybrid repeats in addition to clade-specific Long Interspersed Nuclear Elements (LINE). Equus caballus clade specific LINE 1 (L1) repeats can be classified into approximately five subfamilies, three of which have undergone significant expansion. There are 1115 full-length copies of these equine L1, but of the 103 presumptive active copies, 93 fall within a single subfamily, indicating a rapid recent expansion of this subfamily. We also analysed both interspersed and simple sequence repeats (SSR) genome-wide, finding that some repeat classes are spatially correlated with each other as well as with G+C content and gene density. Based on these spatial correlations, we have confirmed that recently-described ancestral vs. clade-specific genome territories can be defined by their repeat content. The clade-specific Short Interspersed Nuclear Element correlations were scattered over the genome and appear to have been extensively remodelled. In contrast, territories enriched for ancestral repeats tended to be contiguous domains. To determine if the latter territories were evolutionarily conserved, we compared these results with a similar analysis of the human genome, and observed similar ancestral repeat enriched domains. These results indicate that ancestral, evolutionarily conserved mammalian genome territories can be identified on the basis of repeat content alone. Interspersed repeats of different ages appear to be analogous to geologic strata, allowing identification of ancient vs. newly remodelled regions of mammalian genomes.

Systematic screening of sheep skin cDNA libraries for microsatellite sequences

Publisher: S. Karger AG

Date: 2003

DOI: 10.1159/000075729

Abstract: 65,000 sheep skin cDNA clones were gridded in high density on to nylon membranes and screened for (CA) sub n /sub and (GA) sub n /sub repeat containing clones. 296 dinucleotide repeat-containing clones were identified with ∼85% non-redundancy. Clones were single-pass 5′ sequenced and we compared the Expressed Sequence Tag (EST) sequences to the Swiss-Prot database to ascertain their identity and/or putative function. We then aligned the ESTs against the human genomic sequence to determine the locations of human orthologous sequences. Finally, we developed a subset of polymorphic microsatellite markers and positioned them on the ovine linkage map.

A molecular analysis of hyalin - A substrate for cell adhesion in the hyaline layer of the sea urchin embryo

Publisher: Elsevier BV

Date: 1998

DOI: 10.1006/DBIO.1997.8793

Abstract: The hyaline layer of echinoderm embryos is an extraembryonic matrix that functions as a substrate for cell adhesion through early development. The major constituent of the hyaline layer is the protein hyalin, a fibrillar glycoprotein of approximately 330 kDa that multimerizes in the presence of calcium. Here we provide a molecular characterization of hyalin and identify a region of the protein that is important for its function in cell adhesion. Partial hyalin cDNAs were identified from two sea urchin species, Strongylocentrotus purpuratus and Lytechinus variegatus, by screening expression libraries with monoclonal antibodies to hyalin. The cDNAs each encode a tandemly arranged series of conserved repeats averaging 84 amino acids. These hyalin repeats are as similar between the two species as they are to repeats within each species, suggesting a strong functional conservation. Analysis of this repeat shows that it is a unique sequence within the GenBank database with only weak similarity to mucoid protein sequences. The hyalin mRNA is approximately 12 kb in length and is present in developing oocytes coincident with the appearance of cortical granules, the vesicle in which the hyalin protein is specifically packaged. The mRNA is present throughout oogenesis but is rapidly lost at oocyte maturation so that eggs and early embryos have no detectable hyalin mRNA. The hyalin protein, however, remains at relatively constant levels throughout development. Thus, all the hyalin protein present during early development, when no RNA is detectable, is maternally derived and exocytosed from cortical granules at fertilization. Hyalin mRNA reaccumulates in embryos beginning at the mesenchyme blastula stage a RNA gel blot and in situ hybridization analysis of gastrulae and larvae shows a progressive confinement of hyalin mRNA to the aboral ectoderm. Recombinant hyalin containing the tandem repeat region of the protein was expressed in bacteria and is shown to serve as an adhesive substrate, almost equal to that of native hyalin, in cell adhesion assays. This adhesive activity is partially blocked by dilute hyalin monoclonal antibody Tg-HYL to the same extent as that for native hyalin. Thus, this hyalin repeat region appears to contain the ligand for the hyalin cell surface receptor. These data help explain some of the classic functions ascribed to the hyalin protein in early development and now enable investigators to focus on the mechanisms of cell interactions with the hyaline layer.

The effect of compound kushen injection on cancer cells: Integrated identification of candidate molecular mechanisms

Publisher: Public Library of Science (PLoS)

Date: 30-07-2020

DOI: 10.1371/JOURNAL.PONE.0236395

Fractional Deletion Of Compound Kushen Injection, A Natural Compound Mixture, Indicates Cytokine Signaling Pathways Are Critical For Its Perturbation Of The Cell Cycle

Publisher: Cold Spring Harbor Laboratory

Date: 05-11-2018

DOI: 10.1101/462135

Abstract: We have used computational and experimental biology approaches to identify candidate mechanisms of action of a traditional Chinese medicine. Compound Kushen Injection (CKI), in a breast cancer cell line in which CKI causes apoptosis. Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis in MDA-MB-231 cells. Our initial fractionation separated major from minor compounds, and showed that the major compounds accounted for little of the activity of CKI. By systematically perturbing the major compounds in CKI we found that removal of no single major compound could alter the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical compounds with respect to CKI activity. We then used RNA sequencing and transcriptome analysis to correlate compound removal with gene expression and phenotype data. We determined that many compounds in CKI are required for its effectiveness in triggering apoptosis but that significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

Transient Polycomb activity represses developmental genes in growing oocytes

Publisher: Cold Spring Harbor Laboratory

Date: 19-09-2022

DOI: 10.1101/2022.09.18.508436

Abstract: Non-genetic disease inheritance and offspring phenotype is substantially influenced by germline epigenetic programming, including genomic imprinting. Loss of Polycomb Repressive Complex 2 (PRC2) function in oocytes causes non-genetically inherited effects on offspring, including embryonic growth restriction followed by post-natal offspring overgrowth. While PRC2 dependent non-canonical imprinting is likely to contribute, less is known about germline epigenetic programming of non-imprinted genes during oocyte growth. In addition, de novo germline mutations in genes encoding PRC2 lead to overgrowth syndromes in human patients, but the extent to which PRC2 activity is conserved in human oocytes is poorly understood. In this study we identify a discrete period of early oocyte growth during which PRC2 is expressed in mouse growing oocytes. Deletion of Eed during this window led to the de-repression of 343 genes. A high proportion of these were developmental regulators, and the vast majority were not imprinted genes. Many of the de-repressed genes were also marked by the PRC2-dependent epigenetic modification histone 3 lysine 27 trimethylation (H3K27me3) in primary-secondary mouse oocytes, at a time concurrent with PRC2 expression. In addition, we found H3K27me3 was also enriched on many of these genes by the germinal vesicle (GV) stage in human oocytes, strongly indicating that this PRC2 function is conserved in the human germline. However, while the 343 genes were de-repressed in mouse oocytes lacking EED, they were not de-repressed in pre-implantation embryos and lost H3K27me3 during pre-implantation development. This implies that H3K27me3 is a transient feature that represses a wide range of genes in oocytes. Together, these data indicate that EED has spatially and temporally distinct functions in the female germline to repress a wide range of developmentally important genes, and that this activity is conserved in the mouse and human germlines.

bíogo/ncbi: interfaces to NCBI services for the Go language

Publisher: The Open Journal

Date: 25-05-2017

DOI: 10.21105/JOSS.00234

Gene expression in sheep skin and wool (hair)

Publisher: Elsevier BV

Date: 2004

DOI: 10.1016/S0888-7543(03)00210-6

Abstract: We sequenced 2939 ESTs from fetal and adult sheep skin. Stages of gestation were picked to coincide with the major events in skin appendage (wool follicle) formation. Clustering analysis generated a nonredundant set of ESTs 2435 strong (83% nonredundant). Approximately 24% of these gave no hit to NCBI build 29 of the human genome, while 35% were tentatively classified by putative function based on BLASTX hits with a p(N) of <10(-4). In addition to bioinformatics analysis of our ESTs and gene mapping, we have generated a large EST spatial expression data set using in situ hybridization. One thousand one hundred forty-two ESTs have been used for in situ localization about 31% are from adult sheep skin, 39% from late gestation fetal sheep skin, and 30% from midgestation fetal sheep skin. These probes have been used in over 3000 hybridization experiments. In this report, we summarize the results of in situs on adult sheep skin.

Corrigendum: Intelligent techniques using molecular data analysis in leukaemia: An opportunity for personalized medicine support system (BioMed Research International (2017) 2017 (12) DOI: 10.1155/2017/3587309)

Publisher: Hindawi Limited

Date: 21-06-2018

DOI: 10.1155/2018/8208254

Insights and applications from sequencing the bovine genome

Publisher: CSIRO Publishing

Date: 2008

DOI: 10.1071/RD07157

Abstract: Humans have sought to improve/tailor cattle since their domestication a few thousand years ago. Up until the last 40–50 years, consistent genetic improvement of cattle was a hit or miss proposition. Recent progress has been more rapid, thanks to applications of quantitative genetics to breeding schemes. With the availability of the bovine genome sequence, genetic selection and on-farm management are likely to be revolutionised yet again. Genetic association studies that were previously impossible to carry out due to a lack of markers are now possible. In addition to improved genetic mapping of economic traits, the bovine genome sequence allows us to create a common context for genetic and physiological data, which will provide novel insights into gene regulation and function.

Superior ab initio identification, annotation and characterisation of TEs and segmental duplications from genome assemblies

Publisher: Public Library of Science (PLoS)

Date: 14-03-2018

DOI: 10.1371/JOURNAL.PONE.0193588

ARMC5Mutations Are Common in Familial Bilateral Macronodular Adrenal Hyperplasia

Publisher: The Endocrine Society

Date: 09-2014

DOI: 10.1210/JC.2014-1265

Abstract: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing's syndrome. Familial cases have been reported, but at the time we conducted this study, the genetic basis of BMAH was unknown. Recently, germline variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH and somatic, second-hit mutations in tumor nodules, were identified. Our objective was to identify the genetic basis of familial BMAH. We performed whole exome capture and sequencing of 2 affected in iduals from each of 4 BMAH families (BMAH-01, BMAH-02, BMAH-03, and BMAH-05). Based on clinical evaluation, there were 7, 3, 3, and 4 affected in iduals in these families, respectively. Sanger sequencing of ARMC5 was performed in 1 other BMAH kindred, BMAH-06. Exome sequencing identified novel variants Chr16:g.31477540, c.2139delT, p.(Thr715Leufs*1) (BMAH-02) and Chr16:g.31473811, c.943C→T, p.(Arg315Trp) (BMAH-03) in ARMC5 (GRch37/hg19), validated by Sanger sequencing. BMAH-01 had a recently reported mutation Chr16:g.31476121, c.1777C→T, p.(Arg593Trp). Sanger sequencing of ARMC5 in BMAH-06 identified a previously reported mutation, Chr16:g. 31473688 c.799C→T, p.(Arg267*). The genetic basis of BMAH in BMAH-05 was not identified. Our studies have detected ARMC5 mutations in 4 of 5 BMAH families tested, confirming that these mutations are a frequent cause of BMAH. Two of the 4 families had novel mutations, indicating allelic heterogeneity. Preclinical evaluation did not predict mutation status. The ARMC5-negative family had unusual prominent hyperaldosteronism. Further studies are needed to determine the penetrance of BMAH in ARMC5 mutation-positive relatives of affected patients, the practical utility of genetic screening and genotype-phenotype correlations.

A comprehensive genomic history of extinct and living elephants

Publisher: Proceedings of the National Academy of Sciences

Date: 26-02-2018

DOI: 10.1073/PNAS.1720554115

Abstract: Elephantids were once among the most widespread megafaunal families. However, only three species of this family exist today. To reconstruct their evolutionary history, we generated 14 genomes from living and extinct elephantids and from the American mastodon. While previous studies examined only simple bifurcating relationships, we found that gene flow between elephantid species was common in the past. Straight-tusked elephants descend from a mixture of three ancestral populations related to the ancestor of African elephants, woolly mammoths, and present-day forest elephants. We detected interbreeding between North American woolly and Columbian mammoths but found no evidence of recent gene flow between forest and savanna elephants, demonstrating that both gene flow and isolation have been central in the evolution of elephantids.

Horizontal transfer and subsequent explosive expansion of a DNA transposon in sea kraits ( Laticauda )

Publisher: The Royal Society

Date: 09-2021

DOI: 10.1098/RSBL.2021.0342

Abstract: Transposable elements (TEs) are self-replicating genetic sequences and are often described as important ‘drivers of evolution’. This driving force is because TEs promote genomic novelty by enabling rearrangement, and through exaptation as coding and regulatory elements. However, most TE insertions potentially lead to neutral or harmful outcomes, therefore host genomes have evolved machinery to suppress TE expansion. Through horizontal transposon transfer (HTT) TEs can colonize new genomes, and since new hosts may not be able to regulate subsequent replication, these TEs may proliferate rapidly. Here, we describe HTT of the Harbinger-Snek DNA transposon into sea kraits ( Laticauda ), and its subsequent explosive expansion within Laticauda genomes. This HTT occurred following the ergence of Laticauda from terrestrial Australian elapids approximately 15–25 Mya. This has resulted in numerous insertions into introns and regulatory regions, with some insertions into exons which appear to have altered UTRs or added sequence to coding exons. Harbinger-Snek has rapidly expanded to make up 8–12% of Laticauda spp. genomes this is the fastest known expansion of TEs in amniotes following HTT. Genomic changes caused by this rapid expansion may have contributed to adaptation to the hibious-marine habitat.

Modelling predictors of molecular response to frontline imatinib for patients with chronic myeloid leukaemia

Publisher: Public Library of Science (PLoS)

Date: 03-01-2017

DOI: 10.1371/JOURNAL.PONE.0168947

Correction: Comparative GO: A Web Application for Comparative Gene Ontology and Gene Ontology-Based Gene Selection in Bacteria

Publisher: Public Library of Science (PLoS)

Date: 17-04-2015

DOI: 10.1371/JOURNAL.PONE.0125537

The tuatara genome: insights into vertebrate evolution from the sole survivor of an ancient reptilian order

Publisher: Cold Spring Harbor Laboratory

Date: 08-12-2019

DOI: 10.1101/867069

Abstract: The tuatara ( Sphenodon punctatus ), the only living member of the archaic reptilian order Rhynchocephalia (Sphenodontia) once widespread across Gondwana, is an iconic and enigmatic terrestrial vertebrate endemic to New Zealand. A key link to the now extinct stem reptiles from which dinosaurs, modern reptiles, birds and mammals evolved, the tuatara provides exclusive insights into the ancestral amniotes. The tuatara genome, at ∼5 Gbp, is among the largest vertebrate genomes assembled. Analysis of this genome and comparisons to other vertebrates reinforces the uniqueness of the tuatara. Phylogenetic analyses indicate tuatara erged from the snakes and lizards ∼250 MYA. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Genome sequence analysis identifies expansions of protein, non-protein-coding RNA families, and repeat elements, the latter of which show an extraordinary amalgam of reptilian and mammalian features. Sequencing of this genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. It also provides important insights into both the technical challenges and the cultural obligations associated with genome sequencing.

The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms

Publisher: Cold Spring Harbor Laboratory

Date: 21-12-2018

DOI: 10.1101/503318

Abstract: Because Traditional Chinese Medicine (TCM) preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study. Compound Kushen Injection (CKI) is a complex mixture cancer treatment used in Chinese hospitals for over twenty years. To demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways. We used a cancer cell culture model to measure the effect of CKI on cell cycle phases, apoptosis and correlate those phenotypes with CKI induced changes in gene expression. We treated cancer cells with CKI in order to generate and analyse high-throughput transcriptome data from two cancer cell lines. We integrated these differential gene expression results with previously reported results. CKI induced cell-cycle arrest and apoptosis and altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes. By identifying promising candidate pathways and genes associated with CKI based on our transcriptome-based analysis, we have shown this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.

Chinese Herbal Medicine Versus Other Interventions in the Treatment of Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

Publisher: SAGE Publications

Date: 2018

DOI: 10.1177/2515690X18781519

Abstract: Diabetes affects 422 million people and directly caused 4.9 million deaths according to the global report on diabetes in 2014. Type 2 diabetes accounts for 90% of people with diabetes around the world. Chinese herbal medicine treatment for diabetes has more than 2000-year history in China. An increasing number of people around the world are trying to manage type 2 diabetes with Chinese herbal medicine. However, there is a lack of evidence to decide if Chinese herbal medicine is effective and safe when compared with other interventions for the treatment of type 2 diabetes We identified 58 randomized controlled trials involving 6637 participants with type 2 diabetes with trial periods lasting from 8 weeks to 1 year (average 12 weeks). We extracted data following a predefined hierarchy. A total of 132 different Chinese herbal medicines were examined. We included studies comparing Chinese herbal medicine with other interventions and excluded trials that did not satisfy the inclusion criteria. We evaluated primary outcomes of trials in accordance with the Cochrane Handbook for Systematic Reviews of Intervention. Fifty-six out of 58 studies reported evidence that Chinese herbal medicines were effective at controlling blood sugar, insulin resistance, and traditional Chinese medicine clinical symptoms for patients with type 2 diabetes. And outcome variables are summarized. However, the evidence is limited because of the quality of the studies. Well-designed long-term studies with large s les and multiple centers as well as standardization and quality control will be required to determine if Chinese herbal medicine treatment is effective and safe for type 2 diabetes.

Seed weight differences between wild and domesticated soybeans are associated with specific changes in gene expression

Publisher: Springer Science and Business Media LLC

Date: 26-06-2017

DOI: 10.1007/S00299-017-2165-5

Abstract: Our study systematically explored potential genes and molecular pathways as candidates for differences in seed weight resulting from soybean domestication. In addition, potential contributions of lncRNAs to seed weight were also investigated. Soybeans have a long history of domestication in China, and there are several significant phenotypic differences between cultivated and wild soybeans, for ex le, seeds of cultivars are generally larger and heavier than those from wild accessions. We analyzed seed transcriptomes from thirteen soybean s les, including six landraces and seven wild accessions using strand-specific RNA sequencing. Differentially expressed genes related to seed weight were identified, and some of their homologs were associated with seed development in Arabidopsis. We also identified 1251 long intergenic noncoding RNAs (lincRNAs), 243 intronic RNAs and 81 antisense lncRNAs de novo from these soybean transcriptomes. We then profiled the expression patterns of lncRNAs in cultivated and wild soybean seeds, and found that transcript levels of a number of lncRNAs were s le-specific. Moreover, gene transcript and lincRNA co-expression network analysis showed that some soybean lincRNAs might have functional roles as they were hubs of co-expression modules. In conclusion, this study systematically explored potential genes and molecular pathways as candidates for differences in seed weight resulting from soybean domestication, and will provide a useful future resource for molecular breeding of soybeans.

Identification of candidate anti-cancer molecular mechanisms of Compound Kushen Injection using functional genomics

Publisher: Impact Journals, LLC

Date: 09-2016

DOI: 10.18632/ONCOTARGET.11788

Correction: HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

Publisher: Public Library of Science (PLoS)

Date: 29-12-2015

DOI: 10.1371/JOURNAL.PGEN.1005782

Loss of EED in the oocyte causes initial fetal growth restriction followed by placental hyperplasia and offspring overgrowth

Publisher: Cold Spring Harbor Laboratory

Date: 11-08-2022

DOI: 10.1101/2022.08.08.503175

Abstract: Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to placental hyperplasia in mammalian offspring generated by somatic cell nuclear transfer (SCNT). In this study, we show that offspring from mouse oocytes lacking the Polycomb protein Embryonic Ectoderm Development (EED) were initially growth restricted, characterised by low blastocyst cell counts and substantial mid-gestational developmental delay. This initial developmental delay was followed by striking late-gestational placental hyperplasia, fetal catch-up growth and extended gestational length that culminated in offspring overgrowth. This involved remodelling of the placenta, including expansion of fetal and maternal tissues and conspicuous expansion of the glycogen enriched cell population in the junctional zone that was associated with a delay in parturition. Despite this remodelling and offspring catchup growth, fetal lacental weight ratio and fetal blood glucose levels were low indicating low placental efficiency. Genome-wide analyses identified extensive transcriptional dysregulation in affected placentas, including a range of imprinted and non-imprinted genes and increased expression of the H3K27me3-imprinted gene Slc38a4, which regulates transport of essential amino acids in the placenta. Our data provide an explanation for apparently opposing observations of growth restriction and overgrowth of offspring derived from Eed-null oocytes and demonstrate that PRC2-dependent programming in the oocyte regulates fetal and placental growth and developmental outcomes.

Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection

Publisher: Springer Science and Business Media LLC

Date: 24-01-2019

DOI: 10.1186/S12885-018-5230-8

Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse

Publisher: Public Library of Science (PLoS)

Date: 22-10-2013

DOI: 10.1371/JOURNAL.PONE.0078280

The long noncoding RNA FRILAIR regulates strawberry fruit ripening by functioning as a noncanonical target mimic

Publisher: Public Library of Science (PLoS)

Date: 19-03-2021

DOI: 10.1371/JOURNAL.PGEN.1009461

Abstract: Long noncoding RNAs (lncRNAs) are emerging as important regulators in plant development, but few of them have been functionally characterized in fruit ripening. Here, we have identified 25,613 lncRNAs from strawberry ripening fruits based on RNA-seq data from poly(A)-depleted libraries and rRNA-depleted libraries, most of which exhibited distinct temporal expression patterns. A novel lncRNA, FRILAIR harbours the miR397 binding site that is highly conserved in erse strawberry species. FRILAIR overexpression promoted fruit maturation in the Falandi strawberry, which was consistent with the finding from knocking down miR397, which can guide the mRNA cleavage of both FRILAIR and LAC11a (encoding a putative laccase-11-like protein). Moreover, LAC11a mRNA levels were increased in both FRILAIR overexpressing and miR397 knockdown fruits, and accelerated fruit maturation was also found in LAC11a overexpressing fruits. Overall, our study demonstrates that FRILAIR can act as a noncanonical target mimic of miR397 to modulate the expression of LAC11a in the strawberry fruit ripening process.

Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

Publisher: Springer Science and Business Media LLC

Date: 05-04-2011

DOI: 10.1186/1471-2164-12-176

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain. We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124 . We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099 . We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099 , with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development.

Increase in dermal papilla cells by proliferation during development of the primary wool follicle

Publisher: CSIRO Publishing

Date: 1992

DOI: 10.1071/AR9920843

Abstract: The growth of the demand condensate and dermal papilla of developing primary wool follicles was investigated by counting cells in paraffin of foetal sheep skin. The number of cells in the dermal condensate of prepapilla was found to increase approximately two-fold between follicle initiation and maturation (stages F1 and F8). This increase was not continuous but was interrupted by a no growth period from stages F2a to F6. The proportion of iding dermal condensate cells, determined by the BrdU/Anti-BrdU technique, was shown to peak during periods of cell number increase. In addition, we were able to demonstrate that the increase in cell number described above could be accounted for entirely by cell proliferation, with no contribution from migration. The developmental modulation of dermal condensate cell proliferation is discussed in relation to both the Reaction-Diffusion theory of hair follicle initiation and morphogenesis and our current knowledge of the transforming growth factor-G superfamily of proteins.

A comparative analysis of algorithms for somatic SNV detection in cancer

Publisher: Oxford University Press (OUP)

Date: 09-07-2013

DOI: 10.1093/BIOINFORMATICS/BTT375

Abstract: Motivation: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer–normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer–normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm. Results: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned the somatic probability scores assigned to the same sites their susceptibility to various sources of noise and their sensitivities to low-allelic-fraction candidates. Availability: Data accession number SRA081939, code at /snv-caller-review/ Contact: david.adelson@adelaide.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.

Comparative mapping of oculocutaneous albinism type II <i>(OCA2)</i>, transient receptor potential cation channel, subfamily M member 1 <i>(TRPM1)</i> and two equine microsatel

Publisher: S. Karger AG

Date: 2006

DOI: 10.1159/000091935

Genome studies at the PAG 2011 conference

Publisher: Springer Science and Business Media LLC

Date: 03-2011

DOI: 10.1007/S10142-011-0215-6

Abstract: The contents of the plenary lectures presented at the Plant and Animal Genome (PAG) meeting in January 2011 are summarized in order to provide some insights into the advances in plant, animal and microbe genome studies as they impact on our understanding of complex biological systems. The areas of biology covered include the dynamics of genome change, biological recognition processes and the new processes that underpin investment in science. This overview does not attempt to summarize the ersity of activities that are covered during the PAG through workshops, posters and the suppliers of cutting-edge technologies, but reviews major advances in specific research areas.

Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

Publisher: Elsevier BV

Date: 03-2016

DOI: 10.1016/J.YGENO.2016.01.006

Abstract: Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.

A physical map of the bovine genome

Publisher: Springer Science and Business Media LLC

Date: 2007

DOI: 10.1186/GB-2007-8-8-R165

Wool fibre diameter and follicle density are not specified simultaneously during wool follicle initiation

Publisher: CSIRO Publishing

Date: 2002

DOI: 10.1071/AR01200

Abstract: Although the highly negative correlation between wool fibre diameter and wool follicle density has been known for some time, the source of this relationship in terms of the developmental mechanisms involved has been unclear. By comparing follicle rudiment dimensions (measured in the fetus) with fibre diameter values (measured in the same animal as an adult), we present data indicating that this inverse relationship arises largely after follicle initiation. Our data indicate that this is because fibre diameter is largely specified post-initiation, during the period of wool follicle growth and morphogenesis. This result was unexpected, and has permitted us to speculate upon the hierarchy and relationship of genes that control follicle initiation and fibre diameter.

An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci

Publisher: Cold Spring Harbor Laboratory

Date: 12-06-2001

DOI: 10.1101/GR.GR-1350R

Publisher Correction: The tuatara genome reveals ancient features of amniote evolution

Publisher: Springer Science and Business Media LLC

Date: 18-08-2020

DOI: 10.1038/S41586-020-2661-6

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Zuo Gui Wan Alters Expression of Energy Metabolism Genes and Prevents Cell Death in High-Glucose Loaded Mouse Embryos

Publisher: Hindawi Limited

Date: 25-06-2018

DOI: 10.1155/2018/2409471

Abstract: Background . Zuo Gui Wan (ZGW) is a classic formula in traditional chinese medicine (TCM). Previous studies have shown that it is beneficial for impaired glucose tolerance (IGT) of adults and the offspring as well. This study aimed to understand the molecular mechanisms of the efficacy of ZGW on IGT. Methods . We used high-glucose loaded 2-cell stage mouse embryos as a model and took advantage of single-cell RNA sequencing technology to analyze the transcriptome of the model with or without ZGW. Differential gene expression analysis was performed with DESeq2. Results . High glucose can downregulate genes in the ribosome pathway, while ZGW can reverse this inhibition and as a result prevent embryo cell death caused by high glucose. Furthermore, high glucose can affect sugar metabolism and influence mitochondrial function, but ZGW can promote sugar metabolism via the tricarboxylic acid cycle mainly through upregulating the genes in the respiratory chain and oxidative phosphorylation. Conclusions . ZGW had a protective effect on embryonic cell death caused by glucose loading. The reversion of inhibition of ribosome pathway and regulation of mitochondrial energy metabolism are main effects of ZGW on high-glucose loaded embryos. This research not only revealed the global gene regulation changes of high glucose affecting 2-cell stage embryos but also provided insight into the potential molecular mechanisms of ZGW on the IGT model.

Bovine ncRNAs are abundant, primarily intergenic, conserved and associated with regulatory genes

Publisher: Public Library of Science (PLoS)

Date: 06-08-2012

DOI: 10.1371/JOURNAL.PONE.0042638

Understanding the Underlying Mechanism of HA-Subtyping in the Level of Physic-Chemical Characteristics of Protein

Publisher: Public Library of Science (PLoS)

Date: 08-05-2014

DOI: 10.1371/JOURNAL.PONE.0096984

A 1.4-Mb interval RH map of horse chromosome 17 provides detailed comparison with human and mouse homologues

Publisher: Elsevier BV

Date: 02-2004

DOI: 10.1016/J.YGENO.2003.07.002

Abstract: Comparative genomics has served as a backbone for the rapid development of gene maps in domesticated animals. The integration of this approach with radiation hybrid (RH) analysis provides one of the most direct ways to obtain physically ordered comparative maps across evolutionarily erged species. We herein report the development of a detailed RH and comparative map for horse chromosome 17 (ECA17). With markers distributed at an average interval of every 1.4 Mb, the map is currently the most informative among the equine chromosomes. It comprises 75 markers (56 genes and 19 microsatellites), of which 50 gene specific and 5 microsatellite markers were generated in this study and typed to our 5000-rad horse x hamster whole genome RH panel. The markers are dispersed over six RH linkage groups and span 825 cR(5000). The map is among the most comprehensive whole chromosome comparative maps currently available for domesticated animals. It finely aligns ECA17 to human and mouse homologues (HSA13 and MMU1, 3, 5, 8, and 14, respectively) and homologues in other domesticated animals. Comparisons provide insight into their relative organization and help to identify evolutionarily conserved segments. The new ECA17 map will serve as a template for the development of clusters of BAC contigs in regions containing genes of interest. Sequencing of these regions will help to initiate studies aimed at understanding the molecular mechanisms for various diseases and inherited disorders in horse as well as human.

A novel hypothesis-unbiased method for Gene Ontology enrichment based on transcriptome data

Publisher: Public Library of Science (PLoS)

Date: 15-02-2017

DOI: 10.1371/JOURNAL.PONE.0170486

A chromosome inversion near the <i>KIT</i> gene and the Tobiano spotting pattern in horses

Publisher: S. Karger AG

Date: 2007

DOI: 10.1159/000112065

Abstract: Tobiano is a white spotting pattern in horses caused by a dominant gene, i Tobiano /i i (TO) /i . Here, we report i TO /i associated with a large paracentric chromosome inversion on horse chromosome 3. DNA sequences flanking the inversion were identified and a PCR test was developed to detect the inversion. The inversion was only found in horses with the tobiano pattern, including horses with erse genetic backgrounds, which indicated a common genetic origin thousands of years ago. The inversion does not interrupt any annotated genes, but begins approximately 100 kb downstream of the i KIT /i gene. This inversion may disrupt regulatory sequences for the i KIT /i gene and cause the white spotting pattern. This manuscript is accompanied by supplemental figures S1, S2 and S3, as well as supplemental Tables S1 and S2 (oi/10.1159/000112065). The DNA sequence generated in this work has been submitted to GenBank under the following accession number: EF442014.

Evidence for developmentally regulated transcriptional, translational and post-translational control of metallothionein gene expression in hair follicles

Publisher: CSIRO Publishing

Date: 1996

DOI: 10.1071/RD9961089

Abstract: The distribution of metallothionein (MT) and MT mRNAs was examined in hair (wool) follicles, where high levels of cell proliferation are found and where the resulting cells provide a temporal record of differentiation events. MT was found in the cytoplasm and some nuclei of follicle bulb cells of the proliferative zone, outer root sheath cells and in basal layer cells of sebaceous glands and sweat glands. The population of 5-bromo-2'-deoxyuridine (BrdU)+ cells in these tissues overlapped, but were not completely coincident with the distribution of MT staining. MT mRNA expression in hair (wool) follicles was assessed by in situ hybridization with four gene-specific sheep MT (sMT) isoforms. Intense signals were obtained with the sMT-Ib probe in follicle bulb cells from the proliferative zone to the keratogenous zone. Signals from the sMT-Ia probe were present in the same cells, but were much weaker. No signals were detected using the sMT-Ic and sMT-II gene-specific probes. The findings suggest that: (1) MT is important in cell proliferation and/or cell differentiation in the hair follicle bulb (2) MT translation is inhibited during cell differentiation and migration and (3) tissue-specific expression of uncharacterized sMT isoforms is likely.

Mammalian genome evolution as a result of epigenetic regulation of transposable elements

Publisher: Walter de Gruyter GmbH

Date: 06-2014

DOI: 10.1515/BMC-2014-0013

Abstract: Transposable elements (TEs) make up a large proportion of mammalian genomes and are a strong evolutionary force capable of rewiring regulatory networks and causing genome rearrangements. Additionally, there are many eukaryotic epigenetic defense mechanisms able to transcriptionally silence TEs. Furthermore, small RNA molecules that target TE DNA sequences often mediate these epigenetic defense mechanisms. As a result, epigenetic marks associated with TE silencing can be reestablished after epigenetic reprogramming – an event during the mammalian life cycle that results in widespread loss of parental epigenetic marks. Furthermore, targeted epigenetic marks associated with TE silencing may have an impact on nearby gene expression. Therefore, TEs may have driven species evolution via their ability to heritably alter the epigenetic regulation of gene expression in mammals.

Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle

Publisher: Springer Science and Business Media LLC

Date: 02-10-2019

DOI: 10.1038/S41598-019-50271-4

Abstract: We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

Fake IDs? Widespread misannotation of DNA Transposons as a General Transcription Factor

Publisher: Cold Spring Harbor Laboratory

Date: 24-11-2022

DOI: 10.1101/2022.11.24.517799

Abstract: The annotation of transposable elements (TEs) is a critical part of our understanding of genomes, however, the accuracy of annotation pipelines remains an issue as TEs are frequently underestimated or misannotated. We report the General Transcription Factor II-I Repeat Domain-Containing Protein 2 (GTF2IRD2) was used to erroneously annotate DNA transposons in a variety of non-mammalian species as GTF2IRD2 contains a 3’ fused hAT transposase domain. This study emphasises that the misannotation of TEs as trans- regulatory elements, such as transcription factors, can lead to errors in phylogenetic trees based on orthologs and to significant wasted time for investigators interested in gene regulation and characterising non-mammalian genomes.

Widespread of horizontal gene transfer events in eukaryotes

Publisher: Cold Spring Harbor Laboratory

Date: 28-07-2022

DOI: 10.1101/2022.07.26.501571

Abstract: Horizontal gene transfer (HGT) is the transfer of genetic material between distantly related organisms. While most genes in prokaryotes can be horizontally transferred, HGT events in eukaryotes are considered as rare, particularly in mammals. Here we report the identification of HGT regions (HGTs) in 13 model eukaryotes by comparing their genomes with 824 eukaryotic genomes. Between 4 and 358 non-redundant HGTs per species were found in the genomes of 13 model organisms, and most of these HGTs were previously unknown. The majority of the 824 eukaryotes with full length genome sequences also contain HGTs. These HGTs have transformed their host genomes with thousands of copies and have impacted hundreds, even thousands of genes. We extended this analysis to ~128,000 prokaryote and virus genomes and revealed a few potential routes of horizontal gene transfer involving blood sucking parasites, intracellular pathogens, and bacteria. Our findings revealed that HGTs are widespread in eukaryotic genomes, and HGT is a ubiquitous driver of genome evolution for eukaryotes.

The bovine QTL viewer: A web accessible database of bovine Quantitative Trait Loci

Publisher: Springer Science and Business Media LLC

Date: 05-06-2006

DOI: 10.1186/1471-2105-7-283

Abstract: Many important agricultural traits such as weight gain, milk fat content and intramuscular fat (marbling) in cattle are quantitative traits. Most of the information on these traits has not previously been integrated into a genomic context. Without such integration application of these data to agricultural enterprises will remain slow and inefficient. Our goal was to populate a genomic database with data mined from the bovine quantitative trait literature and to make these data available in a genomic context to researchers via a user friendly query interface. The QTL (Quantitative Trait Locus) data and related information for bovine QTL are gathered from published work and from existing databases. An integrated database schema was designed and the database (MySQL) populated with the gathered data. The bovine QTL Viewer was developed for the integration of QTL data available for cattle. The tool consists of an integrated database of bovine QTL and the QTL viewer to display QTL and their chromosomal position. We present a web accessible, integrated database of bovine (dairy and beef cattle) QTL for use by animal geneticists. The viewer and database are of general applicability to any livestock species for which there are public QTL data. The viewer can be accessed at bovineqtl.tamu.edu .

Effect of Compound Kushen Injection, a natural compound mixture, and its identified chemical components on migration and invasion of colon, brain and breast cancer cell lines

Publisher: Cold Spring Harbor Laboratory

Date: 19-12-2018

DOI: 10.1101/500124

Abstract: Cancer metastasis is a major cause of death. Traditional Chinese medicines (TCM) are promising sources of new anti-metastatic agents. Compound Kushen Injection (CKI), extracted from medicinal plants, Kushen (Sophora flavescens) and Baituling (Heterosmilax chinensis), contains a mixture of alkaloids and flavonoids known to disrupt cell cycle and induce apoptosis in breast cancer (MCF7). However, effects on cancer cell migration and invasion have remained unknown. CKI, fractionated mixtures, and single identified components were tested in migration assays with colon (HT-29, SW-480, DLD-1), brain (U-87 MG, U-251 MG), and breast (MDA-MB-231) cancer cell lines. Human embryonic kidney (HEK-293) and human foreskin fibroblast (HFF) served as non-cancerous controls. Wound closure, transwell invasion, and live cell imaging assays showed that CKI reduced motility in all eight cell lines. The greatest inhibition of migration occurred in HT-29 and MDA-MB-231, and the least in HEK-293. Fractionation and reconstitution of CKI showed that combinations of compounds were required for activity. Live cell imaging confirmed CKI strongly reduced migration of HT-29 and MDA-MB-231 cells, moderately slowed brain cancer cells, and had no effect on HEK-293. CKI uniformly blocked invasiveness through extracellular matrix. Apoptosis was increased by CKI in MDA-MB-231 cells but not in non-cancerous cells. Cell viability in CKI was unaffected in all cell lines. Transcriptomic analyses of MDA-MB-231 with and without CKI indicated down-regulated expression of actin cytoskeletal and focal adhesion genes, consistent with the observed impairment of cell migration. The pharmacological complexity of CKI is important for its effective block of cancer cell migration and invasion.

Discovery of a novel long terminal repeat (LTR2i_SS) in Sus Scrofa

Publisher: Wiley

Date: 12-03-2014

DOI: 10.1111/AGE.12138

Abstract: Long terminal repeat (LTR) retrotransposons are transposable elements flanked by 5'/3' LTRs. They have a structure similar to endogenous retroviruses, but they lack the envelope (env) gene making them non-infectious. Long terminal repeats are motif-rich sequences and can act as bidirectional promoters or enhancers to regulate or inactivate genes by insertion. In this study, we identified a new chimeric LTR subfamily, LTR2i_SS, in the pig genome. This chimeric LTR family appears to be the ancestral form of the previously described LTR2_SS family. LTR2_SS appears to have deleted ~300 bp of un-annotated, ancestral sequence from LTR2i_SS. We identified no functional provirus sequences for either of these LTR types. LTR2i_SS sequences have been exapted into the untranslated regions of two protein-coding gene mRNAs. Both of these genes lie within previously mapped pig quantitative trait loci.

Identification of Endometrial Genes Regulated by Early Pregnancy, Progesterone, and Interferon Tau in the Ovine Uterus1

Publisher: Oxford University Press (OUP)

Date: 02-2006

DOI: 10.1095/BIOLREPROD.105.046656

Abstract: During early pregnancy in ruminants, progesterone (P4) from the corpus luteum and interferon tau (IFNT) from the conceptus act on the endometrium to regulate genes important for uterine receptivity and conceptus growth. The use of the uterine gland knockout (UGKO) ewe has demonstrated the critical role of epithelial secretions in regulation of conceptus survival and growth. A custom ovine cDNA array was used to identify alterations in gene expression of endometria from Day 14 cyclic, pregnant, and UGKO ewes (study 1) and from cyclic ewes treated with P4 or P4 with ZK 136,317 antiprogestin and control proteins or IFNT (study 2). In study 1, expression of 47 genes was more than 2-fold different between Day 14 pregnant and cyclic endometria, whereas 23 genes was different between Day 14 cyclic and UGKO endometria. In study 2, 70 genes were different due to P4 alone, 74 genes were affected by IFNT in a P4-dependent manner, and 180 genes were regulated by IFNT in a P4-independent manner. In each study, an approximately equal number of genes were found to be activated or repressed in each group. Endometrial genes increased by pregnancy and P4 and/or IFNT include B2M, CTSL, CXCL10, G1P3, GRP, IFI27, IFIT1, IFITM3, LGALS15, MX1, POSTN, RSAD2, and STAT5A. Transcripts decreased by pregnancy and P4 and/or IFNT include COL3A1, LUM, PTMA, PUM1, RPL9, SPARC, and VIM. Identification and analysis of these hormonally responsive genes will help define endometrial pathways critical for uterine support of peri-implantation conceptus survival, growth, and implantation.

Identification and sequence analysis of chicken Toll-like receptors

Publisher: Springer Science and Business Media LLC

Date: 12-2005

DOI: 10.1007/S00251-004-0740-8

Abstract: Toll-like receptors (TLRs) play an important role in the recognition of microbial components. Only chicken TLR2 and -4 have been reported in the literature. The objectives of this study were to identify new chicken TLRs and to evaluate evolutionary significance of these receptors. Searching chicken genomic databases and DNA sequencing revealed five new TLRs, TLR1 (type 1 and 2), -3, -5, and -7. No chicken orthologues of mammalian TLR8, -9, or -10 were found. As in mammals, all chicken TLRs (chTLRs) share identical protein secondary structure that consists of several leucine-rich domains, a transmembrane domain, and Toll/Interleukin-1 receptor domain(s). Phylogenetic analyses indicate that the identified chTLR genes are the orthologues of TLRs in mammals. Analyses of the number of synonymous substitutions per synonymous site and nonsynonymous substitutions per nonsynonymous site indicate that the nucleotide sequences coding for the leucine-rich repeats of chicken TLR1 type 1 and type 2 were significantly under positive Darwinian selection. In contrast, the sequences of other TLRs were under purifying selection. These results support the hypothesis that one of the major evolutionary strategies of the innate immune system is to recognize a few highly conserved microbial components with several conserved TLRs. The results also indicate that the sequence changes in the ligand-binding domains of TLR1 in chickens provide adaptive advantages during evolution.

Genomic organization, annotation, and ligand-receptor inferences of chicken chemokines and chemokine receptor genes based on comparative genomics

Publisher: Springer Science and Business Media LLC

Date: 24-03-2005

DOI: 10.1186/1471-2164-6-45

A New Strategy for Identifying Mechanisms of Drug-drug Interaction Using Transcriptome Analysis: Compound Kushen Injection as a Proof of Principle

Publisher: Springer Science and Business Media LLC

Date: 04-11-2019

DOI: 10.1038/S41598-019-52375-3

Abstract: Drug-drug interactions (DDIs), especially with herbal medicines, are complex, making it difficult to identify potential molecular mechanisms and targets. We introduce a workflow to carry out DDI research using transcriptome analysis and interactions of a complex herbal mixture, Compound Kushen Injection (CKI), with cancer chemotherapy drugs, as a proof of principle. Using CKI combined with doxorubicin or 5-Fu on cancer cells as a model, we found that CKI enhanced the cytotoxic effects of doxorubicin on A431 cells while protecting MDA-MB-231 cells treated with 5-Fu. We generated and analysed transcriptome data from cells treated with single treatments or combined treatments and our analysis showed that opposite directions of regulation for pathways related to DNA synthesis and metabolism which appeared to be the main reason for different effects of CKI when used in combination with chemotherapy drugs. We also found that pathways related to organic biosynthetic and metabolic processes might be potential targets for CKI when interacting with doxorubicin and 5-Fu. Through co-expression analysis correlated with phenotype results, we selected the MYD88 gene as a candidate major regulator for validation as a proof of concept for our approach. Inhibition of MYD88 reduced antagonistic cytotoxic effects between CKI and 5-Fu, indicating that MYD88 is an important gene in the DDI mechanism between CKI and chemotherapy drugs. These findings demonstrate that our pipeline is effective for the application of transcriptome analysis to the study of DDIs in order to identify candidate mechanisms and potential targets.

Transposable elements and gene expression during the evolution of amniotes

Publisher: Cold Spring Harbor Laboratory

Date: 16-03-2018

DOI: 10.1101/283390

Abstract: Transposable elements (TEs) are primarily responsible for the changes in genome sequences that occur over time within and between species. TEs themselves evolve, with clade specific LTR/ERV, LINEs and SINEs responsible for the bulk of species specific genomic features. Because TEs can contain regulatory motifs, they can be exapted as regulators of gene expression. While TE insertions can provide evolutionary novelty for the regulation of gene expression, their overall impact on the evolution of gene expression is unclear. Previous investigators have shown that tissue specific gene expression in amniotes is more similar across species than within species, supporting the existence of conserved developmental gene regulation. In order to understand how species specific TE insertions might affect the evolution/conservation of gene expression, we have looked at the association of gene expression in six tissues with TE insertions in six representative amniote genomes (human, opossum, platypus, anole lizard, bearded dragon and chicken). We have used a novel bootstrapping approach to minimise the conflation of effects of repeat types on gene expression. We compared the expression of orthologs containing different types of recent TE insertions to orthologs that contained older TE insertions and found significant differences in gene expression associated with TE insertions. Likewise, we compared the expression of non-ortholog genes containing different types of recent TE insertions to non-orthologs with older TE insertions and found significant differences in gene expression associated with TE insertions. As expected TEs were associated with species-specific changes in gene expression, but the magnitude and direction of change of expression changes were unexpected. Overall, orthologs containing clade specific TEs were associated with lower gene expression, while in non-orthologs, non clade-specific TEs were associated with higher gene expression. Exceptions were SINE elements in human and chicken, which had an opposite association with gene expression compared to other species. Our observed species-specific associations of TEs with gene expression support a role for TEs in speciation/response to selection by species. TEs do not exhibit consistent associations with gene expression and observed associations can vary depending on the age of TE insertions. Based on these observations, it would be prudent to refrain from extrapolating these and previously reported associations to distantly related species.

Bovine Genome Database: integrated tools for genome annotation and discovery

Publisher: Oxford University Press (OUP)

Date: 12-2010

DOI: 10.1093/NAR/GKQ1235

Horizontal transposon transfer and its implications for the ancestral ecology of hydrophiine snakes

Publisher: Cold Spring Harbor Laboratory

Date: 23-06-2021

DOI: 10.1101/2021.06.22.449521

Abstract: Transposable elements (TEs), also known as jumping genes, are sequences able to move or copy themselves within a genome. As TEs move throughout genomes they often act as a source of genetic novelty, hence understanding TE evolution within lineages may help in understanding environmental adaptation. Studies into the TE content of lineages of mammals such as bats have uncovered horizontal transposon transfer (HTT) into these lineages, with squamates often also containing the same TEs. Despite the repeated finding of HTT into squamates, little comparative research has examined the evolution of TEs within squamates. Here we examine a erse family of Australo-Melanesian snakes (Hydrophiinae) to examine if the previously identified, order-wide pattern of variable TE content and activity holds true on a smaller scale. Hydrophiinae erged from Asian elapids ∼30 Mya and have since rapidly ersified into six hibious, ∼60 marine and ∼100 terrestrial species which fill a broad range of ecological niches. We find TE ersity and expansion differs between hydrophiines and their Asian relatives and identify multiple HTTs into Hydrophiinae, including three likely transferred into the ancestral hydrophiine from fish. These HTT events provide the first tangible evidence that Hydrophiinae reached Australia from Asia via a marine route.

bíogo: a simple high-performance bioinformatics toolkit for the Go language

Publisher: The Open Journal

Date: 18-02-2017

DOI: 10.21105/JOSS.00167

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Publisher: American Physiological Society

Date: 10-2009

DOI: 10.1152/PHYSIOLGENOMICS.00001.2009

Abstract: Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of preimplantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and preimplantation blastocyst growth and development in sheep.

bíogo/hts: high throughput sequence handling for the Go language

Publisher: The Open Journal

Date: 04-02-2017

DOI: 10.21105/JOSS.00168

Yiqi Chutan Tang Reduces Gefitinib‐Induced Drug Resistance in Non‐Small‐Cell Lung Cancer by Targeting Apoptosis and Autophagy

Publisher: Wiley

Date: 14-08-2019

DOI: 10.1002/CYTO.A.23869

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

Publisher: MDPI AG

Date: 17-03-2017

DOI: 10.3390/IJMS18030656

Re-evaluating inheritance in genome evolution: widespread transfer of LINEs between species

Publisher: Cold Spring Harbor Laboratory

Date: 08-02-2017

DOI: 10.1101/106914

Abstract: Transposable elements (TEs) are mobile DNA sequences, colloquially known as ‘jumping genes’ because of their ability to replicate to new genomic locations. Given a vector of transfer (e.g. tick or virus), TEs can jump further: between organisms or species in a process known as horizontal transfer (HT). Here we propose that LINE-1 (L1) and Bovine-B (BovB), the two most abundant TE families in mammals, were initially introduced as foreign DNA via ancient HT events. Using a 503-genome dataset, we identify multiple ancient L1 HT events in eukaryotes and provide evidence that L1s infiltrated the mammalian lineage after the monotreme-therian split. We also extend the BovB paradigm by increasing the number of estimated transfer events compared to previous studies, finding new potential blood-sucking parasite vectors and occurrences in new lineages (e.g. bats, frog). Given that these TEs make up nearly half of the genome sequence in today’s mammals, our results provide the first evidence that HT can have drastic and long-term effects on the new host genomes. This revolutionizes our perception of genome evolution to consider external factors, such as the natural introduction of foreign DNA. With the advancement of genome sequencing technologies and bioinformatics tools, we anticipate our study to be the first of many large-scale phylogenomic analyses exploring the role of HT in genome evolution. LINE-1 (L1) elements occupy about half of most mammalian genomes (1), and they are believed to be strictly vertically inherited (2). Mutagenic L1 insertions are thought to account for approximately 1 of every 1000 random, disease-causing insertions in humans (4-7). Our research indicates that the very presence of L1s in humans, and other therian mammals, is due to an ancient transfer event – which has drastic implications for our perception of genome evolution. Using a machina analyses over 503 genomes, we trace the origins of L1 and BovB retrotransposons across the tree of life, and provide evidence of their long-term impact on eukaryotic evolution.

Widespread horizontal transfer of retrotransposons

Publisher: Proceedings of the National Academy of Sciences

Date: 31-12-2013

DOI: 10.1073/PNAS.1205856110

Abstract: In higher organisms such as vertebrates, it is generally believed that lateral transfer of genetic information does not readily occur, with the exception of retroviral infection. However, horizontal transfer (HT) of protein coding repetitive elements is the simplest way to explain the patchy distribution of BovB, a long interspersed element (LINE) about 3.2 kb long, that has been found in ruminants, marsupials, squamates, monotremes, and African mammals. BovB sequences are a major component of some of these genomes. Here we show that HT of BovB is significantly more widespread than believed, and we demonstrate the existence of two plausible arthropod vectors, specifically reptile ticks. A phylogenetic tree built from BovB sequences from species in all of these groups does not conform to expected evolutionary relationships of the species, and our analysis indicates that at least nine HT events are required to explain the observed topology. Our results provide compelling evidence for HT of genetic material that has transformed vertebrate genomes.

Characterization and distribution of retrotransposons and simple sequence repeats in the bovine genome

Publisher: Proceedings of the National Academy of Sciences

Date: 04-08-2009

DOI: 10.1073/PNAS.0901282106

Abstract: Interspersed repeat composition and distribution in mammals have been best characterized in the human and mouse genomes. The bovine genome contains typical eutherian mammal repeats, but also has a significant number of long interspersed nuclear element RTE (BovB) elements proposed to have been horizontally transferred from squamata. Our analysis of the BovB repeats has indicated that only a few of them are currently likely to retrotranspose in cattle. However, bovine L1 repeats (L1 BT) have many likely active copies. Comparison of substitution rates for BovB and L1 BT indicates that L1 BT is a younger repeat family than BovB. In contrast to mouse and human, L1 occurrence is not negatively correlated with G+C content. However, BovB, Bov A2, ART2A, and Bov-tA are negatively correlated with G+C, although Bov-tAs correlation is weaker. Also, by performing genome wide correlation analysis of interspersed and simple sequence repeats, we have identified genome territories by repeat content that appear to define ancestral vs. ruminant-specific genomic regions. These ancestral regions, enriched with L2 and MIR repeats, are largely conserved between bovine and human.

The sheep genome illuminates biology of the rumen and lipid metabolism

Publisher: American Association for the Advancement of Science (AAAS)

Date: 06-06-2014

DOI: 10.1126/SCIENCE.1252806

Abstract: Sheep-specific genetic changes underlie differences in lipid metabolism between sheep and other mammals, and may have contributed to the production of wool. Jiang et al. sequenced the genome of two Texel sheep, a breed that produces high-value meat, milk, and wool. The genome information will provide an important resource for livestock production and aid in the understanding of mammalian evolution. Science , this issue p. 1168

Genome-Wide Analysis of the Association of Transposable Elements with Gene Regulation Suggests that Alu Elements Have the Largest Overall Regulatory Impact

Publisher: Mary Ann Liebert Inc

Date: 06-2018

DOI: 10.1089/CMB.2017.0228

Abstract: Nearly half of the human genome is made up of transposable elements (TEs), and there is evidence that TEs are involved in gene regulation. In this study, we have integrated publicly available genomic, epigenetic, and transcriptomic data to investigate this in a genome-wide manner. A bootstrapping statistical method was applied to minimize confounder effects from different repeat types. Our results show that although most TE classes are primarily associated with reduced gene expression, Alu elements are associated with upregulated gene expression. Furthermore, Alu elements had the highest probability of any TE class contributing to regulatory regions of any type defined by chromatin state. This suggests a general model where clade-specific short interspersed elements (SINEs) may contribute more to gene regulation than ancient/ancestral TEs. Our exhaustive analysis has extended and updated our understanding of TEs in terms of their global impact on gene regulation and suggests that the most recently derived types of TEs, that is, clade- or species-specific SINES, have the greatest overall impact on gene regulation.

MicroRNAs Are Part of the Regulatory Network that Controls EGF Induced Apoptosis, Including Elements of the JAK/STAT Pathway, in A431 Cells

Publisher: Public Library of Science (PLoS)

Date: 17-03-2015

DOI: 10.1371/JOURNAL.PONE.0120337

Transcription of nuclear organellar DNA in a model plant system

Publisher: Oxford University Press (OUP)

Date: 27-05-2014

DOI: 10.1093/GBE/EVU111

Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression

Publisher: Bioscientifica

Date: 10-2017

DOI: 10.1530/REP-16-0586

Abstract: This study aimed to define the expression patterns of HENMT1 and PIWI proteins in human testis and investigate their association with transposon expression, infertility sub-type or development of testicular germ cell tumours (TGCTs). Testis biopsies showing normal spermatogenesis were used to identify normal localisation patterns of HENMT1 and PIWIL1 by immunolocalisation and RT-PCR after laser microdissection. 222 testis biopsies representing normal spermatogenesis, hypospermatogenesis, spermatogenic arrests, Sertoli cell-only (SCO) tumours and TGCTs were analysed by RT-qPCR for expression of HENMT1/PIWIL1/PIWIL2/PIWIL3/PIWIL4 and LINE-1 . Additionally, HENMT1 -overexpressing TCam2 seminoma cell lines were analysed for the same parameters by RT-qPCR. We found that HENMT1 and PIWIL1 are coexpressed in pachytene spermatocytes and spermatids. Expression of HENMT1 , PIWIL1 and PIWIL2 was mainly dependent on germ cell content but low levels of expression were also detected in some SCO s les. Levels of HENMT1 , PIWIL1 and PIWIL2 expression were low in TGCT. S les with HENMT1, PIWIL2 and PIWIL4 expression showed significantly ( P 0.05) lower transposon expression compared to s les without expression in the same histological group. HENMT1-overexpressing TCam2 cells showed lower LINE-1 expression than empty vector-transfected control lines. Our findings support that the transposon-regulating function of the piRNA pathway found in the mouse is conserved in adult human testis. HENMT1 and PIWI proteins are expressed in a germ-cell-specific manner and required for transposon control.

Annotation of the chicken IL10 gene cluster and effects of lipopolysaccharide stimulation on IL10 gene expression

Publisher: Wiley

Date: 06-2005

DOI: 10.1111/J.1365-2052.2005.01264.X

Accelerated brain aging towards transcriptional inversion in a zebrafish model of familial Alzheimer’s disease

Publisher: Cold Spring Harbor Laboratory

Date: 09-02-2018

DOI: 10.1101/262162

Abstract: Alzheimer’s disease (AD) develops silently over decades. We cannot easily access and analyse pre-symptomatic brains, so the earliest molecular changes that initiate AD remain unclear. Previously, we demonstrated that the genes mutated in early-onset, dominantly-inherited familial forms of AD (fAD) are evolving particularly rapidly in mice and rats. Fortunately, some non-mammalian vertebrates such as the zebrafish preserve fAD-relevant transcript isoforms of the PRESENILIN ( PSEN1 and PSEN2 ) genes that these rodents have lost. Zebrafish are powerful vertebrate genetic models for many human diseases, but no genetic model of fAD in zebrafish currently exists. We edited the zebrafish genome to model the unique, protein-truncating fAD mutation of human PSEN2 , K115fs. Analysing the brain transcriptome and proteome of young (6-month-old) and aged, infertile (24-month-old) wild type and heterozygous fAD-like mutant female sibling zebrafish supports accelerated brain aging and increased glucocorticoid signalling in young fAD-like fish, leading to a transcriptional ‘inversion’ into glucocorticoid resistance and vast changes in biological pathways in aged, infertile fAD-like fish. Notably, one of these changes involving microglia-associated immune responses regulated by the ETS transcription factor family is preserved between our zebrafish fAD model and human early-onset AD. Importantly, these changes occur before obvious histopathology and likely in the absence of Aβ. Our results support the contributions of early metabolic and oxidative stresses to immune and stress responses favouring AD pathogenesis and highlight the value of our fAD-like zebrafish genetic model for elucidating early changes in the brain that promote AD pathogenesis. The success of our approach has important implications for future modelling of AD.

Assignment of the <i>Equus caballus</i> interleukin 8 gene <i>(IL8)</i> to chromosome 3q14.2→q14.3 by in situ hybridization

Publisher: S. Karger AG

Date: 2006

DOI: 10.1159/000089892

Transposable elements and gene expression during the evolution of amniotes

Publisher: Springer Science and Business Media LLC

Date: 12-06-2018

DOI: 10.1186/S13100-018-0124-5

Effect of compound kushen injection, a natural compound mixture, and its identified chemical components on migration and invasion of colon, brain, and breast cancer cell lines

Publisher: Frontiers Media SA

Date: 26-04-2019

DOI: 10.3389/FONC.2019.00314

Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance

Publisher: Springer Science and Business Media LLC

Date: 20-09-2018

DOI: 10.1186/S12915-018-0569-5

Retrotransposons: Genomic and Trans-Genomic Agents of Change

Publisher: Springer International Publishing

Date: 2015

DOI: 10.1007/978-3-319-19932-0_4

Chromosomal Assignment of Six Genes (EIF4G3, HSP90, RBBP6, IL8, TERT, andTERC) in Four Species of the GenusEquus

Publisher: Informa UK Limited

Date: 07-2011

DOI: 10.1080/10495398.2011.575300

Abstract: We mapped six genes (EIF4G3, HSP90, RBBP6, IL8, TERT, and TERC) on the chromosomes of Equus caballus, Equus asinus, Equus grevyi, and Equus burchelli by fluorescence in situ hybridization. Our results add six type I markers to the cytogenetic map of these species and provide new information on the comparative genomics of the genus Equus.

A 2.5-Mb contig constructed from Angus, Longhorn and horned Hereford DNA spanning the polled interval on bovine chromosome 1

Publisher: Wiley

Date: 21-11-2006

DOI: 10.1111/J.1365-2052.2006.01538.X

Abstract: The polled locus has been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. As an intermediate step in our efforts to identify the polled locus and the underlying causative mutation for the polled phenotype, we have constructed a BAC-based physical map of the interval containing the polled locus. Clones containing genes and markers in the critical interval were isolated from the TAMBT (constructed from Angus and Longhorn genomic DNA) and CHORI-240 (constructed from horned Hereford genomic DNA) BAC libraries and ordered based on fingerprinting and the presence or absence of 80 STS markers. A single contig spanning 2.5 Mb was assembled. Comparison of the physical order of STSs to the corresponding region of human chromosome 21 revealed the same order of genes within the polled critical interval. This contig of overlapping BAC clones from horned and polled breeds is a useful resource for SNP discovery and characterization of positional candidate genes.

Divergent genome evolution caused by regional variation in DNA gain and loss between human and mouse

Publisher: Public Library of Science (PLoS)

Date: 20-04-2018

DOI: 10.1371/JOURNAL.PCBI.1006091

A new strategy for identifying mechanisms of drug-drug interaction using transcriptome analysis: Compound Kushen injection as a proof of principle

Publisher: Cold Spring Harbor Laboratory

Date: 30-03-2019

DOI: 10.1101/592956

Abstract: Drug-drug interactions (DDIs), especially with herbal medicines, are complex, making it difficult to identify potential molecular mechanisms and targets. We introduce a workflow to carry out DDI research using transcriptome analysis and interactions of a complex herbal mixture, Compound Kushen Injection (CKI), with cancer chemotherapy drugs, as a proof of principle. Using CKI combined with doxorubicin or 5-Fu on cancer cells as a model, we found that CKI enhanced the cytotoxic effects of doxorubicin on A431 cells while protecting MDA-MB-231 cells treated with 5-Fu. We generated and analysed transcriptome data from cells treated with single treatments or combined treatments and our analysis showed that opposite directions of regulation for pathways related to DNA synthesis and metabolism appeared to be the main reason for different effects of CKI when used in combination with chemotherapy drugs. We also found that pathways related to organic biosynthetic and metabolic processes might be potential targets for CKI when interacting with doxorubicin and 5-Fu. Through co-expression analysis correlated with phenotype results, we selected the MYD88 gene as a candidate major regulator for validation as a proof of concept for our approach. Inhibition of MYD88 reduced antagonistic cytotoxic effects between CKI and 5-Fu, indicating that MYD88 is an important gene in the DDI mechanism between CKI and chemotherapy drugs. These findings demonstrate that our pipeline is effective for the application of transcriptome analysis to the study of DDIs in order to identify candidate mechanisms and potential targets.

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

Publisher: Hindawi Limited

Date: 2017

DOI: 10.1155/2017/3587309

Abstract: The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient’s genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

Evolutionary conservation and functional roles of ncRNA

Publisher: Frontiers Media SA

Date: 2012

DOI: 10.3389/FGENE.2012.00205

Long read reference genome-free reconstruction of a full-length transcriptome from Astragalus membranaceus reveals transcript variants involved in bioactive compound biosynthesis

Publisher: Springer Science and Business Media LLC

Date: 29-08-2017

DOI: 10.1038/CELLDISC.2017.31

Abstract: Astragalus membranaceus, also known as Huangqi in China, is one of the most widely used medicinal herbs in Traditional Chinese Medicine. Traditional Chinese Medicine formulations from Astragalus membranaceus have been used to treat a wide range of illnesses, such as cardiovascular disease, type 2 diabetes, nephritis and cancers. Pharmacological studies have shown that immunomodulating, anti-hyperglycemic, anti-inflammatory, antioxidant and antiviral activities exist in the extract of Astragalus membranaceus . Therefore, characterising the biosynthesis of bioactive compounds in Astragalus membranaceus , such as Astragalosides, Calycosin and Calycosin-7-O-β- d -glucoside, is of particular importance for further genetic studies of Astragalus membranaceus . In this study, we reconstructed the Astragalus membranaceus full-length transcriptomes from leaf and root tissues using PacBio Iso-Seq long reads. We identified 27 975 and 22 343 full-length unique transcript models in each tissue respectively. Compared with previous studies that used short read sequencing, our reconstructed transcripts are longer, and are more likely to be full-length and include numerous transcript variants. Moreover, we also re-characterised and identified potential transcript variants of genes involved in Astragalosides, Calycosin and Calycosin-7-O-β- d -glucoside biosynthesis. In conclusion, our study provides a practical pipeline to characterise the full-length transcriptome for species without a reference genome and a useful genomic resource for exploring the biosynthesis of active compounds in Astragalus membranaceus .

Horizontal transfer and subsequent explosive expansion of a DNA transposon in sea kraits (Laticauda)

Publisher: Cold Spring Harbor Laboratory

Date: 14-06-2021

DOI: 10.1101/2021.06.13.448261

Abstract: Transposable elements (TEs) are self replicating genetic sequences and are often described as important “drivers of evolution”. This driving force is because TEs promote genomic novelty by enabling rearrangement, and through exaptation as coding and regulatory elements. However, most TE insertions will be neutral or harmful, therefore host genomes have evolved machinery to supress TE expansion. Through horizontal transposon transfer (HTT) TEs can colonise new genomes, and since new hosts may not be able to shut them down, these TEs may proliferate rapidly. Here we describe HTT of the Harbinger-Snek DNA transposon into sea kraits ( Laticauda ), and its subsequent explosive expansion within Laticauda genomes. This HTT occurred following the ergence of Laticauda from terrestrial Australian elapids ~15-25 Mya. This has resulted in numerous insertions into introns and regulatory regions, with some insertions into exons which appear to have altered UTRs or added sequence to coding exons. Harbinger-Snek has rapidly expanded to make up 8-12% of Laticauda spp. genomes this is the fastest known expansion of TEs in amniotes following HTT. Genomic changes caused by this rapid expansion may have contributed to adaptation to the hibious-marine habitat.

Jumping between Turtles, Fishes, and a Frog: The Unexpected Horizontal Transfer of a DNA Transposon

Publisher: Cold Spring Harbor Laboratory

Date: 21-08-2023

DOI: 10.1101/2023.08.19.550906

Abstract: Horizontal transfer of transposable elements (HTT) has been reported across many species and the impact of such events on genome structure and function has been well described. However, few studies have focused on reptilian genomes, especially HTT events in Testudines (turtles). Here, we investigated the repetitive content of Malaclemys terrapin terrapin (Diamondback turtle) and found a high similarity hAT-6 DNA transposon shared between other turtle species, ray-finned fishes, and a frog. hAT-6 was notably absent in taxa closely related to turtles, such as crocodiles and birds. Successful invasion of DNA transposons into new genomes requires the conservation of specific residues in the encoded transposase, and through structural analysis, these residues were identified indicating retention of functional transposition activity. We document a rare and recent HTT event of a DNA transposon between turtles which are known to have a low genomic evolutionary rate and ancient repeats.

An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer

Publisher: Elsevier BV

Date: 10-2019

DOI: 10.1016/J.BIOPHA.2019.109169

Abstract: Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.

Similar Evolutionary Trajectories for Retrotransposon Accumulation in Mammals

Publisher: Oxford University Press (OUP)

Date: 09-2017

DOI: 10.1093/GBE/EVX179

USDA stakeholder workshop on animal bioinformatics: Summary and recommendations

Publisher: No publisher found

Date: 2003

DOI: 10.1002/CFG.266

In vivo effects of epidermal growth factor on epidermal pattern formation and hair follicle initiation in the marsupial bandicoot Isoodon macrourus

Publisher: CSIRO Publishing

Date: 1997

DOI: 10.1071/R96118

Abstract: The extrauterine development of marsupial pouch young (northern brown bandicoot Isoodon macrourus) has facilitated the study of the effects of murine epidermal growth factor (mEGF) on pattern formation in skin. Hair follicle initiation and development, which in the mouse would occur from about Days 13–14 of gestation onward, occurs postnatally. In the present study the effect in vivo of mEGF on developing skin corresponding to mouse gestational ages from Day 13 onward was examined. Subcutaneous injections of mEGF (0· 5, 1 ·0 and 2· 0 µg g-1 body weight) or equivalent volumes of saline (0· 9% w/w) were administered daily, before and during hair follicle initiation and development. Murine EGF inhibited the formation of hair follicles, hair follicle sweat glands, sebaceous glands and dermal papillae. The pattern of follicle initiation was perturbed. The characteristic trio follicle grouping was absent, and follicle rudiment densities (no. per mm2skin surface) were significantly lower in animals treated with mEGF, whereas follicle diameters were increased. These data may reflect a role for the epidermal growth factor (EGF) receptor in epidermal pattern formation. The EGF receptor and its potential ligands (such as EGF, transforming growth factor (TGF-α) or other yet-to-be-discovered ligands) perhaps act as parts of a pattern-forming system in vertebrate skin. Extra keyword: EGF receptor.

Chromosomal assignments and sequences for the equine core circadian clock genes

Publisher: Wiley

Date: 11-01-2007

DOI: 10.1111/J.1365-2052.2006.01549.X

Correction to: Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis (Apoptosis, (2013), 18, 11, (1291-1305), 10.1007/s10495-013-0887-6)

Publisher: Springer Science and Business Media LLC

Date: 12-12-2018

DOI: 10.1007/S10495-017-1431-X

Abstract: The original version of this article unfortunately contained a mistake. The affiliation of first author Dr. Ibrahim Alanazi was incorrect.

Identification and Comparative Analysis of ncRNAs in Human, Mouse and Zebrafish Indicate a Conserved Role in Regulation of Genes Expressed in Brain

Publisher: Public Library of Science (PLoS)

Date: 20-12-2012

DOI: 10.1371/JOURNAL.PONE.0052275

LINEs between Species: Evolutionary Dynamics of LINE-1 Retrotransposons across the Eukaryotic Tree of Life

Publisher: Oxford University Press (OUP)

Date: 03-10-2016

DOI: 10.1093/GBE/EVW243

Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy

Publisher: Springer Science and Business Media LLC

Date: 02-2015

DOI: 10.1038/MP.2014.189

Abstract: Cerebral palsy (CP) is a common, clinically heterogeneous group of disorders affecting movement and posture. Its prevalence has changed little in 50 years and the causes remain largely unknown. The genetic contribution to CP causation has been predicted to be ~2%. We performed whole-exome sequencing of 183 cases with CP including both parents (98 cases) or one parent (67 cases) and 18 singleton cases (no parental DNA). We identified and validated 61 de novo protein-altering variants in 43 out of 98 (44%) case-parent trios. Initial prioritization of variants for causality was by mutation type, whether they were known or predicted to be deleterious and whether they occurred in known disease genes whose clinical spectrum overlaps CP. Further, prioritization used two multidimensional frameworks-the Residual Variation Intolerance Score and the Combined Annotation-dependent Depletion score. Ten de novo mutations in three previously identified disease genes (TUBA1A (n=2), SCN8A (n=1) and KDM5C (n=1)) and in six novel candidate CP genes (AGAP1, JHDM1D, MAST1, NAA35, RFX2 and WIPI2) were predicted to be potentially pathogenic for CP. In addition, we identified four predicted pathogenic, hemizygous variants on chromosome X in two known disease genes, L1CAM and PAK3, and in two novel candidate CP genes, CD99L2 and TENM1. In total, 14% of CP cases, by strict criteria, had a potentially disease-causing gene variant. Half were in novel genes. The genetic heterogeneity highlights the complexity of the genetic contribution to CP. Function and pathway studies are required to establish the causative role of these putative pathogenic CP genes.

HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

Publisher: Public Library of Science (PLoS)

Date: 23-10-2015

DOI: 10.1371/JOURNAL.PGEN.1005620

Differential allelic representation (DAR) identifies candidate eQTLs and improves transcriptome analysis

Publisher: Cold Spring Harbor Laboratory

Date: 02-03-2023

DOI: 10.1101/2023.03.02.530865

Abstract: In comparisons between mutant and wild-type genotypes, transcriptome analysis can reveal the direct impacts of a mutation, together with the homeostatic responses of the biological system. Recent studies have highlighted that, when homozygous mutations are studied in non-isogenic backgrounds, genes from the same chromosome as a mutation often appear over-represented among differentially expressed (DE) genes. One hypothesis suggests that DE genes chromosomally linked to a mutation may not reflect true biological responses to the mutation but, instead, result from differences in representation of expression quantitative trait loci (eQTLs) between s le groups selected on the basis of mutant or wild-type genotype. This is problematic when inclusion of spurious DE genes in a functional enrichment study results in incorrect inferences of mutation effect. Here we show that chromosomally co-located differentially expressed genes (CC-DEGs) can also be observed in analyses of dominant mutations in heterozygotes. We define a method and a metric to quantify, in RNA-sequencing data, localised differential allelic representation (DAR) between groups of s les subject to differential expression analysis. We show how the DAR metric can predict regions prone to eQTL-driven differential expression, and how it can improve functional enrichment analyses through gene exclusion or weighting of gene-level rankings. Advantageously, this improved ability to identify probable eQTLs also reveals ex les of CC-DEGs that are likely to be functionally related to a mutant phenotype. This supports a long-standing prediction that selection for advantageous linkage disequilibrium influences chromosome evolution. By comparing the genomes of zebrafish ( Danio rerio ) and medaka ( Oryzias latipes ), a teleost with a conserved ancestral karyotype, we find possible ex les of chromosomal aggregation of CC-DEGs during evolution of the zebrafish lineage. The DAR metric provides a solid foundation for addressing the eQTL issue in new and existing datasets because it relies solely on RNA-sequencing data.

Horizontal transfer of BovB and L1 retrotransposons in eukaryotes

Publisher: Springer Science and Business Media LLC

Date: 09-07-2018

DOI: 10.1186/S13059-018-1456-7

QTL global meta-analysis: Are trait determining genes clustered?

Publisher: Springer Science and Business Media LLC

Date: 2009

DOI: 10.1186/1471-2164-10-184

Characterization of the equine 2′-5′ oligoadenylate synthetase 1 (OAS1) and ribonuclease L (RNASEL) innate immunity genes

Publisher: Springer Science and Business Media LLC

Date: 07-09-2007

DOI: 10.1186/1471-2164-8-313

Abstract: The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies. Genomic sequence for equine OAS1 was obtained from a contig assembly generated from a shotgun subclone library of CHORI-241 BAC 100I10. Specific lification of regions of the OAS1 gene from 13 horses of various breeds identified 33 single nucleotide polymorphisms (SNP) and two microsatellites. RNASEL cDNA sequences were determined for 8 mammals and utilized in a phylogenetic analysis. The chromosomal location of the RNASEL gene was assigned by FISH to ECA5p17-p16 using two selected CHORI-241 BAC clones. The horse genomic RNASEL sequence was assembled. Specific lification of regions of the RNASEL gene from 13 horses identified 31 SNPs. In this report, two dinucleotide microsatellites and 64 single nucleotide polymorphisms within the equine OAS1 and RNASEL genes were identified. These polymorphisms are the first to be reported for these genes and will facilitate future case-control studies of horse susceptibility to infectious diseases.

Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse

Publisher: American Association for the Advancement of Science (AAAS)

Date: 06-11-2009

DOI: 10.1126/SCIENCE.1178158

Abstract: The history of horse domestication is closely tied to the history of the human society. Wade et al. (p. 865 ) report on the sequencing and provide a single nucleotide polymorphism map of the horse ( Equus caballus ) genome. Horses are a member of the order perissodactyla (odd-toed animals with hooves). The analysis reveals an evolutionarily new centromere on equine chromosome 11 that displays properties of an immature but fully functioning centromere and is devoid of centromeric satellite sequence. The findings clarify the nature of genetic ersity within and across horse breeds and suggest that the horse was domesticated from a relatively large number of females, but few males.

Copy Number Variation in the Horse Genome

Publisher: Public Library of Science (PLoS)

Date: 23-10-2014

DOI: 10.1371/JOURNAL.PGEN.1004712

Genome stability is in the eye of the beholder: recent retrotransposon activity varies significantly across avian diversity

Publisher: Cold Spring Harbor Laboratory

Date: 14-04-2021

DOI: 10.1101/2021.04.13.439746

Abstract: Since the sequencing of the zebra finch genome it has become clear the avian genome, while largely stable in terms of chromosome number and gene synteny, is more dynamic at an intrachromosomal level. A multitude of intrachromosomal rearrangements and significant variation in transposable element content have been noted across the avian tree. Transposable elements (TEs) are a source of genome plasticity, because their high similarity enables chromosomal rearrangements through non-allelic homologous recombination, and they have potential for exaptation as regulatory and coding sequences. Previous studies have investigated the activity of the dominant TE in birds, CR1 retrotransposons, either focusing on their expansion within single orders, or comparing passerines to non-passerines. Here we comprehensively investigate and compare the activity of CR1 expansion across orders of birds, finding levels of CR1 activity vary significantly both between and with orders. We describe high levels of TE expansion in genera which have speciated in the last 10 million years including kiwis, geese and Amazon parrots low levels of TE expansion in songbirds across their ersification, and near inactivity of TEs in the cassowary and emu for millions of years. CR1s have remained active over long periods of time across most orders of neognaths, with activity at any one time dominated by one or two families of CR1s. Our findings of higher TE activity in species-rich clades and dominant families of TEs within lineages mirror past findings in mammals. Transposable elements (TEs) are mobile, self replicating DNA sequences within a species’ genome, and are ubiquitous sources of mutation. The dominant group of TEs within birds are chicken repeat 1 (CR1) retrotransposons, making up 7-10% of the typical avian genome. Because past research has examined the recent inactivity of CR1s within model birds such as the chicken and the zebra finch, this has fostered an erroneous view that all birds have low or no TE activity on recent timescales. Our analysis of numerous high quality avian genomes across multiple orders identified both similarities and significant differences in how CR1s expanded. Our results challenge the established view that TEs in birds are largely inactive and instead suggest that their variation in recent activity may contribute to lineage-specific changes in genome structure. Many of the patterns we identify in birds have previously been seen in mammals, highlighting parallels between the evolution of birds and mammals.

Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2

Publisher: Public Library of Science (PLoS)

Date: 24-01-2020

DOI: 10.1371/JOURNAL.PONE.0227258

In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

Publisher: Elsevier BV

Date: 06-2016

DOI: 10.1016/J.DIB.2016.01.045

New Environment, New Invaders—Repeated Horizontal Transfer of LINEs to Sea Snakes

Publisher: Oxford University Press (OUP)

Date: 06-10-2020

DOI: 10.1093/GBE/EVAA208

Abstract: Although numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species, we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Ma. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar LINEs present in fish and marine invertebrates. The one exception was a similar LINE found in sea kraits, a lineage of hibious elapids which independently transitioned to a marine environment 25 Ma. Our finding of repeated horizontal transfer events into marine snakes greatly expands past findings that the marine environment promotes the transfer of transposons. Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. We identified 13 candidate genes for HTT-induced adaptive change based on internal or neighboring HTT LINE insertions. One of these, ADCY4, is of particular interest as a part of the KEGG adaptation pathway “Circadian Entrainment.” This provides evidence of the ecological interactions between species influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.

Horizontal Transposon Transfer and Its Implications for the Ancestral Ecology of Hydrophiine Snakes

Publisher: MDPI AG

Date: 25-01-2022

DOI: 10.3390/GENES13020217

Abstract: Transposable elements (TEs), also known as jumping genes, are sequences able to move or copy themselves within a genome. As TEs move throughout genomes they often act as a source of genetic novelty, hence understanding TE evolution within lineages may help in understanding environmental adaptation. Studies into the TE content of lineages of mammals such as bats have uncovered horizontal transposon transfer (HTT) into these lineages, with squamates often also containing the same TEs. Despite the repeated finding of HTT into squamates, little comparative research has examined the evolution of TEs within squamates. Here we examine a erse family of Australo–Melanesian snakes (Hydrophiinae) to examine if the previously identified, order-wide pattern of variable TE content and activity holds true on a smaller scale. Hydrophiinae erged from Asian elapids ~30 Mya and have since rapidly ersified into six hibious, ~60 marine and ~100 terrestrial species that fill a broad range of ecological niches. We find TE ersity and expansion differs between hydrophiines and their Asian relatives and identify multiple HTTs into Hydrophiinae, including three likely transferred into the ancestral hydrophiine from fish. These HTT events provide the first tangible evidence that Hydrophiinae reached Australia from Asia via a marine route.

The tuatara genome reveals ancient features of amniote evolution

Publisher: Springer Science and Business Media LLC

Date: 05-08-2020

DOI: 10.1038/S41586-020-2561-9

Abstract: The tuatara ( Sphenodon punctatus )—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana 1,2 —is an iconic species that is endemic to New Zealand 2,3 . A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes 2,4 . Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage erged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.

Galectin 15 (LGALS15): A Gene Uniquely Expressed in the Uteri of Sheep and Goats that Functions in Trophoblast Attachment1

Publisher: Oxford University Press (OUP)

Date: 12-2007

DOI: 10.1095/BIOLREPROD.107.063594

Abstract: Galectins are a family of secreted animal lectins with biological roles in cell adhesion and migration. In sheep, galectin 15 (LGALS15) is expressed specifically in the endometrial luminal (LE) and superficial glandular (sGE) epithelia of the uterus in concert with blastocyst elongation during the peri-implantation period. The present study examined LGALS15 expression in the uterus of cattle, goats, and pigs. Although the bovine genome contains an LGALS15-like gene, expressed sequence tags encoding LGALS15 mRNA were found only for sheep, and full-length LGALS15 cDNAs were cloned only from endometrial total RNA isolated from pregnant sheep and goats, but not pregnant cattle or pigs. Ovine and caprine LGALS15 were highly homologous at the mRNA (95%) and protein (91%) levels, and all contained a conserved carbohydrate recognition domain and RGD recognition sequence for integrin binding. Endometrial LGALS15 mRNA levels increased after Day 11 of both the estrous cycle and pregnancy, and were considerably increased after Day 15 of pregnancy in goats. In situ hybridization detected abundant LGALS15 mRNA in endometrial LE and sGE of early pregnant goats, but not in cattle or pigs. Immunoreactive LGALS15 protein was present in endometrial epithelia and conceptus trophectoderm of goat uteri and detected within intracellular crystal structures in trophectoderm and LE. Recombinant ovine and caprine LGALS15 proteins elicited a dose-dependent increase in ovine trophectoderm cell attachment in vitro that was comparable to bovine fibronectin. These results support the hypothesis that LGALS15 is uniquely expressed in Caprinae endometria and functions as an attachment factor important for peri-implantation blastocyst elongation.

A functional genomics catalogue of activated transcription factors during pathogenesis of pneumococcal disease

Publisher: Springer Science and Business Media LLC

Date: 08-09-2014

DOI: 10.1186/1471-2164-15-769

New environment, new invaders - repeated horizontal transfer of LINEs to sea snakes

Publisher: Cold Spring Harbor Laboratory

Date: 28-02-2020

DOI: 10.1101/2020.02.27.968685

Abstract: While numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Mya. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. Such major shifts in habitat should require significant genomic changes.The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake ( Aipysurus laevis ) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar transposons present in fish and marine invertebrates. The one exception was a similar transposon found in sea kraits, a lineage of hibious elapids which independently transitioned to a marine environment following their ergence from terrestrial species 25 Mya. Our finding of repeated horizontal transfer events into separate lineages of marine snakes greatly expands past findings of frequent horizontal transfer in the marine environment, suggesting it is ideal for the transfer of transposons.Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. This provides evidence of the environment influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.

Chromosomal level genome assembly of medicinal plant Sophora flavescens

Publisher: Springer Science and Business Media LLC

Date: 29-08-2023

DOI: 10.1038/S41597-023-02490-8

Abstract: Sophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). In this study, we used third-generation Nanopore long-read sequencing technology combined with Hi-C scaffolding technology to de novo assemble the S. flavescens genome. We obtained a chromosomal level high-quality S. flavescens draft genome. The draft genome size is approximately 2.08 Gb, with more than 80% annotated as Transposable Elements (TEs), which have recently and rapidly proliferated. This genome size is ~5x larger than its closest sequenced relative Lupinus albus L . . We annotated 60,485 genes and examined their expression profiles in leaf, stem and root tissues, and also characterised the genes and pathways involved in the biosynthesis of major bioactive compounds, including alkaloids, flavonoids and isoflavonoids. The assembled genome highlights the very different evolutionary trajectories that have occurred in recently erged Fabaceae, leading to smaller duplicated genomes.

OAS1 polymorphisms are associated with susceptibility to West Nile encephalitis in horses

Publisher: Public Library of Science (PLoS)

Date: 07-05-2010

DOI: 10.1371/JOURNAL.PONE.0010537

Molecular characterization of the Rocky Mountain elk (Cervus elaphus nelsoni) PRNP putative promoter

Publisher: Oxford University Press (OUP)

Date: 14-09-2007

DOI: 10.1093/JHERED/ESM091

Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting deer (Odocoileus spp.), moose (Alces alces), and Rocky Mountain elk (Cervus elaphus nelsoni). Leucine homozygosity at elk PRNP codon 132 has been associated with reduced CWD susceptibility. However, naturally acquired CWD has been detected in elk possessing the 132 Leu/Leu genotype. Recent human and bovine studies indicate that PRNP regulatory polymorphisms may also influence TSE occurrence. Therefore, we generated sequences for the elk PRNP putative promoter (2.2 kb), exon 1 (predicted 54 bp), intron 1 (predicted 193 bp), and exon 3 (771 bp). Promoter prediction analysis using CpGProD yielded a single elk PRNP promoter that was homologous to regions of known promoter activity in cow and sheep. Molecular interrogation of the elk PRNP putative promoter revealed 32 diallelic single-nucleotide polymorphisms (SNPs). No variation was detected within the predicted exon 1 or intron 1 sequences. Evaluation of elk PRNP exon 3 revealed 3 SNPs (63Y, 312R, 394W-->Met/Leu). Bayesian haplotype reconstruction resulted in 3 elk PRNP haplotypes, with complete linkage disequilibrium observed between all PRNP putative promoter SNPs and codon 132. The results of this study provide the initial genomic foundation for future comparative and haplotype-based elk PRNP studies.

The genome of medicinal plantSophora flavescenshas undergone significant expansion of both transposons and genes

Publisher: Cold Spring Harbor Laboratory

Date: 23-03-2023

DOI: 10.1101/2023.03.20.533393

Abstract: Sophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). However, there is little genomic information available for S. flavescens . In this study, we used third-generation Nanopore long-read sequencing technology combined with Hi-C scaffolding technology to de novo assemble the S. flavescens genome. We obtained a chromosomal level high-quality S. flavescens draft genome. The draft genome size is approximately 2.08 Gb, with more than 80% annotated as Transposable Elements (TEs), which have recently and rapidly proliferated. This genome size is ∼5x larger than its closest sequenced relative Lupinus albus l. . We annotated 60,485 genes and examined their expression profiles in leaf, stem and root tissues, and also characterised the genes and pathways involved in the biosynthesis of major bioactive compounds, including alkaloids, flavonoids and isoflavonoids. The assembled genome highlights the very different evolutionary trajectories that have occurred in recently erged Fabaceae, leading to smaller duplicated genomes vs larger genomes resulting from TE expansion. Our assembly provides valuable resources for conservation, genetic research and breeding of S. flavescens .

Comparative GO: A Web Application for Comparative Gene Ontology and Gene Ontology-Based Gene Selection in Bacteria

Publisher: Public Library of Science (PLoS)

Date: 11-03-2013

DOI: 10.1371/JOURNAL.PONE.0058759

Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm

Publisher: Proceedings of the National Academy of Sciences

Date: 17-05-2004

DOI: 10.1073/PNAS.0402669101

Abstract: Secretions of the uterus support survival and growth of the conceptus (embryo/fetus and associated membranes) during pregnancy. Galectin-15, also known as OVGAL11 and a previously uncharacterized member of the galectin family of secreted β-galactoside lectins containing a conserved carbohydrate recognition domain and a separate putative integrin binding domain, was discovered in the uterus of sheep. In endometria of cyclic and pregnant sheep, galectin-15 mRNA was expressed specifically in the endometrial luminal epithelium but not in the conceptus. In pregnant sheep, galectin-15 mRNA expression appeared in the epithelia between days 10 and 12 and increased between days 12 and 16. Progesterone induced and IFN-τ stimulated galectin-15 mRNA in the endometrial epithelium. Galectin-15 protein was concentrated near and on the apical surface of the endometrial luminal epithelia and localized within discrete cytoplasmic crystalline structures of conceptus trophectoderm (Tr). In the uterine lumen, secreted galectin-15 protein increased between days 14 and 16 of pregnancy. Galectin-15 protein was functional in binding lactose and mannose sugars and immunologically identical to the unnamed M r 14,000 (14K) protein from the ovine uterus that forms crystalline inclusion bodies in endometrial epithelia and conceptus Tr. Based on the functional studies of other galectins, galectin-15 is hypothesized to function extracellularly to regulate Tr migration and adhesion to the endometrial epithelium and intracellularly to regulate Tr cell survival, growth, and differentiation. Galectins may be useful as cellular and molecular markers for endometrial function and receptivity, to enhance conceptus survival and development, and to evaluate and enhance fertility.

A Transcription Factor Contributes to Pathogenesis and Virulence in Streptococcus pneumoniae

Publisher: Public Library of Science (PLoS)

Date: 13-08-2013

DOI: 10.1371/JOURNAL.PONE.0070862

Improved Part-of-Speech Prediction in Suffix Analysis

Publisher: Public Library of Science (PLoS)

Date: 04-10-2013

DOI: 10.1371/JOURNAL.PONE.0076042

Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection with Transcriptome Analysis

Publisher: Cold Spring Harbor Laboratory

Date: 31-03-2019

DOI: 10.1101/592964

Abstract: Herbal compatibility is the knowledge of which herbs to combine in traditional Chinese medicine (TCM) formulations. The lack of understanding of herbal compatibility is one of the key problems for the application and popularization of TCM in western society. Because of the chemical complexity of herbal medicines, it is simpler to begin to conduct compatibility research based on herbs rather than component plant secondary metabolites. We have used transcriptome analysis to explore the effects and interactions of two plant extracts (Kushen and Baituling) combined in Compound Kushen Injection (CKI). Based on shared chemical compounds and in vitro cytotoxicity comparisons, we found that both the major compounds in CKI, and the cytotoxicity effects of CKI were mainly derived from the extract of Kushen ( Sophorae flavescentis ). We generated and analyzed transcriptome data from MDA-MB-231 cells treated with single-herb extracts or CKI and results showed that Kushen contributed to the perturbation of the majority of cytotoxicity/cancer related pathways in CKI such as cell cycle and DNA replication. We also found that Baituling ( Heterosmilax yunnanensis Gagnep ) could not only enhance the cytotoxic effects of Kushen in CKI, but also activate immune-related pathways. Our analyses predicted that IL-1 β gene expression was upregulated by Baituling in CKI and we confirmed that IL-1 β protein expression was increased using an ELISA assay. Altogether, these findings help to explain the rationale for combining Kushen and Baituling in CKI, and transcriptome analysis using single herb extracts is an effective method for understanding herbal compatibility in TCM.

Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β‐catenin signaling pathway

Publisher: Wiley

Date: 24-03-2019

DOI: 10.1002/PTR.6347

Abstract: Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.

Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics

Publisher: Springer Science and Business Media LLC

Date: 09-07-2015

DOI: 10.1038/SREP10940

Abstract: Biological and biomedical research relies on comprehensive understanding of protein-coding transcripts. However, the total number of human proteins is still unknown due to the prevalence of alternative splicing. In this paper, we detected 31,566 novel transcripts with coding potential by filtering our ab initio predictions with 50 RNA-seq datasets from erse tissues/cell lines. PCR followed by MiSeq sequencing showed that at least 84.1% of these predicted novel splice sites could be validated. In contrast to known transcripts, the expression of these novel transcripts were highly tissue-specific. Based on these novel transcripts, at least 36 novel proteins were detected from shotgun proteomics data of 41 breast s les. We also showed L1 retrotransposons have a more significant impact on the origin of new transcripts/genes than previously thought. Furthermore, we found that alternative splicing is extraordinarily widespread for genes involved in specific biological functions like protein binding, nucleoside binding, neuron projection, membrane organization and cell adhesion. In the end, the total number of human transcripts with protein-coding potential was estimated to be at least 204,950.

Jumping the fine LINE between species: Horizontal transfer of transposable elements in animals catalyses genome evolution

Publisher: Wiley

Date: 03-09-2013

DOI: 10.1002/BIES.201300072

Abstract: Horizontal transfer (HT) is the transmission of genetic material between non-mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely ergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non-LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution.

Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis

Publisher: Springer Science and Business Media LLC

Date: 28-07-2013

DOI: 10.1007/S10495-013-0887-6

Abstract: A431 cells, derived from epidermoid carcinoma, overexpress the epidermal growth factor receptor (EGFR) and when treated with a high dose of EGF will undergo apoptosis. We exploited microarray and proteomics techniques and network prediction to study the regulatory mechanisms of EGF-induced apoptosis in A431 cells. We observed significant changes in gene expression in 162 genes, approximately evenly split between pro-apoptotic and anti-apoptotic genes and identified 30 proteins from the proteomic data that had either pro or anti-apoptotic annotation. Our correlation analysis of gene expression and proteome modeled a number of distinct sub-networks that are associated with the onset of apoptosis, allowing us to identify specific pathways and components. These include components of the interferon signalling pathway, and down stream components, including cytokines and suppressors of cytokine signalling. A central component of almost all gene expression sub-networks identified was TP53, which is mutated in A431 cells, and was down regulated. This down regulation of TP53 appeared to be correlated with proteomic sub-networks of cytoskeletal or cell adhesion components that might induce apoptosis by triggering cytochrome C release. Of the only three genes also differentially expressed as proteins, only serpinb1 had a known association with apoptosis. We confirmed that up regulation and cleavage of serpinb1 into L-DNAaseII was correlated with the induction of apoptosis. It is unlikely that a single pathway, but more likely a combination of pathways is needed to trigger EGF induced apoptosis in A431cells.

Bovine Genome Architecture

Publisher: Wiley

Date: 11-04-2012

DOI: 10.1002/9781118301739.CH10

University Of Adelaide

Location: No location found

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University Of Adelaide

Location: Australia

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Discovery Projects - Grant ID: DP120101703

Start Date: 2012

End Date: 12-2014

Amount: $344,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100181

Start Date: 03-2012

End Date: 12-2015

Amount: $650,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100234

Start Date: 07-2011

End Date: 07-2012

Amount: $430,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0991985

Start Date: 09-2010

End Date: 12-2013

Amount: $500,000.00

Funder: Australian Research Council