ORCID Profile
0000-0001-7480-3197
Current Organisation
Tufts University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 22-08-2008
DOI: 10.1002/AJMG.B.30688
Publisher: Public Library of Science (PLoS)
Date: 28-11-2012
Publisher: Oxford University Press (OUP)
Date: 06-12-2007
DOI: 10.1093/HMG/DDM358
Abstract: The KIAA0319 gene has been recently associated with developmental dyslexia and shown to be involved in neuronal migration. The deduced KIAA0319 protein contains several polycystic kidney disease (PKD) domains which may mediate the interaction between neurons and glial fibres during neuronal migration. We have previously reported the presence of several alternative splicing variants, some of which are predicted to affect the deduced protein. In this study, we over-expressed constructs containing the main form (A) and two alternative variants (B and C) of KIAA0319. We show that the full-length KIAA0319 (A) is a type I plasma membrane protein, a topology consistent with its proposed function in neuronal migration. The oligomeric status of KIAA0319 is mainly dimeric, and this condition depends on the cysteine-rich regions of the protein, especially the transmembrane (TM) domain and surrounding sequence. KIAA0319 is highly glycosylated in different mammalian cell lines. The central region including the PKD domains is N-glycosylated. Furthermore, a short fragment N-terminal to the PKD domains contains mucin-type O-glycosylation. The two alternative isoforms are soluble proteins lacking the TM domain and, interestingly, only isoform B is secreted. KIAA0319-deletion proteins lacking the TM domain were also secreted. These results suggest that KIAA0319 could be involved not only in cell-cell interactions, but also in signalling.
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: EXT1 and EXT2 are two genes responsible for the majority of cases of hereditary multiple exostoses (HME), a dominantly inherited bone disorder. In order to develop an efficient screening strategy for mutations in these genes, we performed two independent blind screens of EXT1 and EXT2 in 34 unrelated patients with HME, using denaturing high-performance liquid chromatography (DHPLC) and fluorescent single-strand conformation polymorphism analysis (F-SSCP). The mutation likely to cause HME was found in 29 (85%) of the 34 probands: in 22 of these (76%), the mutation was in EXT1 seven patients (24%) had EXT2 mutations. Nineteen of these disease mutations have not been previously reported. Of the 42 different licon variants identified in total in the cohort, 40 were detected by DHPLC and 39 by F-SSCP. This corresponds to mutation detection efficiencies of 95% and 93% respectively. We have also found that we can confidently distinguish between different sequence variants in the same fragment using F-SSCP but not DHPLC. In light of this, and the similarly high sensitivities of the two techniques, we propose to continue screening with F-SSCP.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-08-2022
Abstract: The use of spoken and written language is a fundamental human capacity. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in s les of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2007
DOI: 10.1038/NG1985
Publisher: Wiley
Date: 04-2003
DOI: 10.1002/MDS.10361
Abstract: Chorea-acanthocytosis is a rare autosomal recessive disorder. Its characteristics are orofacial dyskinesia, hyporeflexia, seizures, aberrant behavior, atrophy of the caudate and putamen, and acanthocytes in the blood with a normal level of lipoproteins. We describe three families with chorea-acanthocytosis. The inheritance pattern was recessive and the average age at onset was 27 years (range, 18-35 years). The presenting symptoms were seizures, aberrant behaviour, chorea, tics, and/or abnormal gait. Phase-contrast and electron microscopy examinations of blood showed 10 to 40% acanthocytes. The lipid profile was normal except that, in one family, no prebetalipoprotein bands corresponding to the fraction of very low-density lipoprotein were seen in high-resolution lipoprotein electrophoresis. Magnetic resonance imaging of the brain showed marked atrophy in the caudate and putamen 18-fluorodeoxyglucose positron emission tomography scan showed hypometabolism in the striatum. In all three families, the disease was linked to a 6-cM region of chromosome 9q21 flanked by the recombinant markers GATA 89a11 and D9S1843. This finding strongly suggests the involvement of a single locus for this syndrome. Three different homozygous mutations of this gene have been identified. Although the clinical presentation was variable, the genetic studies on these three Saudi Arabian families with chorea-acanthocytosis provide strong evidence for a genetic locus for chorea-acanthocytosis at chromosome 9q21.
Publisher: Springer Science and Business Media LLC
Date: 24-10-2007
Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1046/J.0022-202X.2001.01675.X
Abstract: Hailey-Hailey disease is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Mutations in ATP2C1, the gene encoding a novel, P-type Ca2+-transport ATPase, were recently found to cause Hailey-Hailey disease. In this study, we used conformation-sensitive gel electrophoresis to screen all 28 translated exons of ATP2C1 in 24 Hailey-Hailey disease families and three sporadic cases with the disorder. We identified 22 different mutations, 18 of which have not previously been reported, in 25 probands. The novel mutations comprise three nonsense, six insertion/deletion, three splice-site, and six missense mutations and are distributed throughout the ATP2C1 gene. Six mutations were found in multiple families investigated here or in our previous study. Haplotype analysis revealed that two of these are recurrent mutations that have not been inherited from a common ancestor. Comparison between genotype and phenotype in 23 families failed to yield any clear correlation between the nature of the mutation and clinical features of Hailey-Hailey disease. The extensive interfamilial and intrafamilial phenotypic variability observed suggests that modifying genes and/or environmental factors may greatly influence the clinical features of this disease.
Publisher: Springer Berlin Heidelberg
Date: 2008
Publisher: Wiley
Date: 19-10-2010
Publisher: Oxford University Press (OUP)
Date: 1992
DOI: 10.1093/HMG/1.8.579
Abstract: The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK genes.
Publisher: Wiley
Date: 08-2005
DOI: 10.1111/J.1528-1167.2005.65804.X
Abstract: Choreoacanthocytosis (ChAc) is an autosomal recessive disorder caused by mutations in VPS13A on chromosome 9q21 and characterized by neurodegeneration and red cell acanthocytosis. Seizures are not uncommon in ChAc but have not been well characterized in the literature. We report two ChAc families in which patients presented with temporal lobe epilepsy. Detailed medical and family histories were obtained. EEG, video-telemetry, brain magnetic resonance imaging (MRI) with volumetric studies of amygdala and hippoc us, as well as neuropsychological testing were performed. Blood smears were examined for acanthocytosis. Mutation analysis of VPS13A was carried out in five patients. Six patients in three sibships were initially seen with seizures. Age at seizure onset ranged from 22 to 38 years. Seizures preceded other clinical manifestations of ChAc by < or = 15 years. The epileptic aura consisted of a sensation of déjà-vu, fear, hallucinations, palpitations, or vertigo. EEG with video-telemetry showed epileptiform discharges originating either from one or both temporal lobes. Epilepsy was generally well controlled, but some patients had periods of increased seizure frequency requiring treatment with multiple antiepileptic drugs (AEDs). Both families shared a deletion of exons 70-73 of VPS13A, extending to exons 6-7 of GNA14. Temporal lobe epilepsy may be the presenting feature of ChAc and may delay its diagnosis. Epilepsy in ChAc patients represents a challenge, because seizures may at times be difficult to control, and some AEDs may worsen the involuntary movements. Mutations in VPS13A or GNA14 or both may be associated with clinical features of temporal lobe epilepsy.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-09-2010
DOI: 10.1126/SCITRANSLMED.3001267
Abstract: Mutations of the X-linked gene PTCHD1 are associated with autism spectrum disorders and intellectual disability.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2012
DOI: 10.1038/EJHG.2012.73
Publisher: Public Library of Science (PLoS)
Date: 12-09-2013
Publisher: Springer Science and Business Media LLC
Date: 14-10-2011
Publisher: American Medical Association (AMA)
Date: 11-2007
DOI: 10.1001/ARCHNEUR.64.11.1661
Abstract: Choreoacanthocytosis (CHAC) (Online Mendelian Inheritance in Man accession No. 200150) is a hereditary neurodegenerative syndrome characterized by movement disorders, cognitive decline, myopathy, behavioral changes, and acanthocytosis and is caused by mutations in the VPS13A gene. To describe the cases of 2 Mexican women with clinical and molecular characteristics compatible with CHAC. Case reports. Patients Choreoacanthocytosis was identified in 2 Mexican mestizo sisters with healthy consanguineous parents. Clinical manifestations began at different ages. The onset of signs and symptoms of CHAC in the proband was at age 32 years and was characterized by balancing problems followed by chorea, compulsive lip and tongue biting with buccolingual self-mutilation, dysarthria, dysphagia, and weight loss. The first clinical manifestations in the proband's sister occurred at age 45 years and included multiple motor and verbal tics, with coprolalia, followed by lip and tongue biting, self-mutilation, and chorea. The clinical findings in both sisters were remarkable for acanthocytosis that developed late, when neurologic changes were already evident. Mutation screening of the VPS13A gene revealed homozygosity for the frameshift mutation c.3556_3557dupAC in exon 33. Currently, the proband's sister, in whom neurologic defects developed 13 years after onset of CHAC in the proband, is the least affected. The same mutation of the VPS13A gene can be expressed differently in the same family. This observation confirms the notion that there is considerable heterogeneity in the clinical manifestation of CHAC.
Publisher: Oxford University Press (OUP)
Date: 04-1998
DOI: 10.1093/HMG/7.4.737
Abstract: We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2009
DOI: 10.1038/EJHG.2009.47
Publisher: Oxford University Press (OUP)
Date: 07-2003
DOI: 10.1093/HMG/DDG166
Abstract: The Menkes disease gene encodes a P-type transmembrane ATPase (ATP7A) that translocates cytosolic copper ions across intracellular membranes of compartments along the secretory pathway. ATP7A moves from the trans-Golgi network (TGN) to the cell surface in response to exogenously added copper ions and recycles back to the TGN upon copper removal. The protein contains a C-terminal di-leucine motif necessary for internalization from the cell surface. In this study we show that ATP7A is internalized by a novel pathway that is independent of clathrin-mediated endocytosis. Expression of dominant-negative mutants of the dynamin-I, dynamin-II and Eps15 proteins that block clathrin-dependent endocytosis of the transferrin receptor do not inhibit internalization of endogenous ATP7A, or an ATP7A reporter molecule (CD8-MCF1). Similarly, inhibitors of caveolae-mediated uptake do not affect ATP7A internalization whilst preventing uptake of PODIPY-ganglioside GM(1), a caveolae marker. In contrast, expression of a constitutively active mutant of the Rac1 GTPase inhibits plasma membrane internalization of both the ATP7A and transferrin receptor transmembrane proteins. These findings define a novel route required for ATP7A internalization and delivery to endosomes.
Publisher: Elsevier
Date: 2006
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 09-2004
DOI: 10.1302/0301-620X.86B7.14815
Abstract: We performed a prospective genotype-phenotype study using molecular screening and clinical assessment to compare the severity of disease and the risk of sarcoma in 172 in iduals (78 families) with hereditary multiple exostoses. We calculated the severity of disease including stature, number of exostoses, number of surgical procedures that were necessary, deformity and functional parameters and used molecular techniques to identify the genetic mutations in affected in iduals. Each arm of the genotype-phenotype study was blind to the outcome of the other. Mutations EXT1 and EXT2 were almost equally common, and were identified in 83% of in iduals. Non-parametric statistical tests were used. There was a wide variation in the severity of disease. Children under ten years of age had fewer exostoses, consistent with the known age-related penetrance of this condition. The severity of the disease did not differ significantly with gender and was very variable within any given family. The sites of mutation affected the severity of disease with patients with EXT1 mutations having a significantly worse condition than those with EXT2 mutations in three of five parameters of severity (stature, deformity and functional parameters). A single sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1 mutation carriers. There was no evidence that sarcomas arose more commonly in families in whom the disease was more severe. The sarcoma risk in EXT1 carriers is similar to the risk of breast cancer in an older population subjected to breast-screening, suggesting that a role for regular screening in patients with hereditary multiple exostoses is justifiable.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/J.TCB.2003.10.008
Abstract: Transmembrane domain (TMD) proteins comprise a major group of proteins that perform a wide range of functions and act to translate extracellular signals to intracellular responses. They include G-protein coupled receptors (GPCRs), growth factor receptors, ion channels, transporters and metabolic enzymes. In this review, we focus on the current understanding of trafficking of mutant membrane proteins in human disease and speculate on therapeutic strategies.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2009
DOI: 10.1038/MP.2009.34
Publisher: Informa UK Limited
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 31-07-2007
Publisher: Wiley
Date: 29-07-2004
DOI: 10.1002/ANA.20200
Abstract: Chorea-acanthocytosis (ChAc) is a severe, neurodegenerative disorder that shares clinical features with Huntington's disease and McLeod syndrome. It is caused by mutations in VPS13A, which encodes a large protein called chorein. Using antichorein antisera, we found expression of chorein in all human cells analyzed. However, chorein expression was absent or noticeably reduced in ChAc patient cells, but not McLeod syndrome and Huntington's disease cells. This suggests that loss of chorein expression is a diagnostic feature of ChAc.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2005
Abstract: Autism is a severe neurodevelopmental disorder with a complex genetic predisposition. Linkage findings from several genome scans suggest the presence of an autism susceptibility locus on chromosome 2q24-q33, making this region the focus of candidate gene and association studies. Recently, significant association with autism has been reported for single-nucleotide polymorphisms (SNPs) in the SLC25A12 and CMYA3 genes on chromosome 2q. We attempted to replicate these findings in the collection of families from the International Molecular Genetic Study of Autism Consortium (IMGSAC), using the transmission disequilibrium test and case-control comparison. Our study failed to reveal any significant association for the SNPs tested at either locus, suggesting that these variants are unlikely to play a major role in genetic susceptibility to autism in our s le.
Publisher: Springer Science and Business Media LLC
Date: 12-11-2008
Publisher: American Medical Association (AMA)
Date: 04-2005
DOI: 10.1001/ARCHNEUR.62.4.611
Abstract: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. To describe the early clinical features and possible genotype-phenotype correlation in CHAC. Case series in a tertiary care center. PATIENTS AND MAIN OUTCOME METHODS: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.
Publisher: Elsevier BV
Date: 09-2004
DOI: 10.1016/J.YGENO.2004.04.012
Abstract: The gene mutated in chorea-acanthocytosis (CHAC approved gene symbol VPS13A) encodes chorein, a protein similar to yeast Vps13p. We detected several similar putative human proteins by BLAST analysis of chorein. We characterized the structure of three new genes encoding these CHAC-similar proteins, located on chromosomes 1p36, 8q22, and 15q21. The most similar gene in yeast to all four human genes is Vps13, and therefore the human genes were named VPS13A (CHAC, 9q21), VPS13B (8q22), VPS13C (15q21), and VPS13D (1p36). VPS13B has recently been reported as COH1, altered in Cohen syndrome. For each gene, we describe several alternative splicing variants at least two transcripts per gene are major forms. The expression pattern of these genes is ubiquitous, with some tissue-specific differences between several transcript variants. Protein sequence comparisons suggest that intramolecular duplications have played an important role in the evolution of this gene family.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2005
DOI: 10.1007/S10048-005-0220-9
Abstract: Mutations in VPS13A cause chorea-acanthocytosis (ChAc), an autosomal recessive neurodegenerative disorder. VPS13A is located in a tail-to-tail arrangement with GNA14 on chromosome 9q21. ChAc shows substantial allelic heterogeneity, with no single VPS13A mutation causing the majority of cases. We examined 11 patients in four French Canadian ChAc pedigrees for mutations in VPS13A. Affected members of three families were homozygous for a 37-kb deletion of the four terminal exons of VPS13A (EX70_EX73del). This deletion also encompasses the two terminal exons of GNA14. Two affected females in family 4 were homozygous for the splicing mutation 4242+1G>T. Remarkably, the affected males in this highly consanguineous pedigree were compound heterozygotes for EX70_EX73del and 4242+1G>T. PCR analysis of the deletion breakpoint junction revealed that an additional patient with French Canadian ancestry was heterozygous for the EX70_EX73del allele. The identification of a common 9q21 haplotype associated with EX70_EX73del in at least four apparently unrelated ChAc families implies that ChAc shows a founder effect in French Canadians, and that routine testing for EX70_EX73del in suspected ChAc cases may therefore be worthwhile in this population. The deletion breakpoint PCR described here will enable rapid identification of both homozygous and heterozygous carriers of EX70_EX73del.
Publisher: Elsevier BV
Date: 03-1995
DOI: 10.1016/0888-7543(95)80089-5
Abstract: The loci involved in several X-linked mental retardation syndromes have been linked to the pericentromeric region of the X chromosome long arm (Xq12-q21). To isolate candidate genes for these diseases, we set up the construction of YAC contigs spanning this region. Two of these syndromes (the Juberg-Marsidi syndrome and the alpha-thalessemia mental retardation syndrome) have been recently linked, with high lod scores, to polymorphic probes previously assigned to Xq13.3. We therefore constructed a first YAC contig, encompassing this band, from DXS441 to PGK1. The physical map, deduced from the isolated clones, extends over 2.1 Mb of genomic DNA. Restriction analysis of the YAC contig allowed us to map precisely the loci previously assigned to that chromosomal region and to define their relative order. The validity of this physical map has been checked by comparing Sfi I digests of the YACs to genomic fragments obtained with the same enzyme. A cDNA selection approach, already performed with a previous partial contig, has been extended to cover the whole region.
Publisher: Oxford University Press (OUP)
Date: 12-04-2000
DOI: 10.1093/HMG/9.7.1131
Abstract: Hailey-Hailey disease (HHD) is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Previous genetic linkage studies localized the gene to a 5 cM interval on human chromosome 3q21. After reducing the disease critical region to <1 cM, we used a positional cloning strategy to identify the gene ATP2C1, which is mutated in HHD. ATP2C1 encodes a new class of P-type Ca(2+)-transport ATPase, which is the homologue for the rat SPLA and the yeast PMR1 medial Golgi Ca(2+)pumps and is related to the sarco(endo)plasmic calcium ATPase (SERCA) and plasma membrane calcium ATPase (PCMA) families of Ca(2+)pumps. The predicted protein has the same apparent transmembrane organization and contains all of the conserved domains present in other P-type ATPases. ATP2C1 produces two alternative splice variants of approximately 4.5 kb encoding predicted proteins of 903 and 923 amino acids. We identified 13 different mutations, including nonsense, frameshift insertion and deletions, splice-site mutations, and non-conservative missense mutations. This study demonstrates that defects in ATP2C1 cause HHD and together with the recent identification of ATP2A2 as the defective gene in Darier's disease, provide further evidence of the critical role of Ca(2+)signaling in maintaining epidermal integrity.
Publisher: Elsevier BV
Date: 05-2014
Publisher: Oxford University Press (OUP)
Date: 11-2002
Abstract: The Menkes disease protein (ATP7A or MNK) is a P-type transmembrane ATPase that regulates translocation of cytosolic copper ions across intracellular membranes of compartments along the secretory pathway. In this study, we show that endogenous MNK in cultured cell lines is localized to the distal Golgi apparatus and translocates to the plasma membrane in response to exogenous copper ions. This transport event is not blocked by expression of a dominant-negative mutant protein kinase D, an enzyme implicated in regulating constitutive trafficking from the trans-Golgi network (TGN) to the plasma membrane, whereas constitutive transport of CD4 is inhibited. In contrast, protein kinase A inhibitors block copper-stimulated MNK delivery to the plasma membrane. Expression of constitutively active Rho GTPases such as Cdc42, Rac1 and RhoA reveals a requirement for Cdc42 in the trafficking of MNK, to the cell surface. Furthermore, overexpression of WASp inhibits anterograde transport of MNK, further supporting regulation by the Cdc42 GTPase. These findings define a novel step in TGN-to-plasma membrane traffic required to export MNK to the cell surface.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2007
DOI: 10.1007/S00335-007-9051-3
Abstract: The KIAA0319 gene in chromosome 6p22 has been strongly associated with developmental dyslexia. In this article we show a wide expression pattern of this gene in human adult brain by Northern blot analysis. We also performed RT-PCR analysis to detect alternative splicing variants in human brain. Most of the detected variants involve alternative splicing of the exons at the 5' and the 3' ends. Two main forms differing in the length of the 5' UTR are detected at approximately the same rate. Two variants (B and C) lacking exon 19, which encodes the transmembrane domain, are the main alternative forms detected among those predicted to encode protein. These two variants could be secreted and might be involved in signaling functions. A similar RT-PCR analysis performed in mouse and rat adult brains showed that only some of the alternative splicing variants are equivalent to those found in the human gene.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Anthony Monaco.