The GALNS p.P77R variant is a probable Gujarati-Indian founder mutation causing Mucopolysaccharidosis IVA syndrome
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB51874 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9451600_1.fastq.gz | Fastqsanger.gz | |||
| ERR9451600_2.fastq.gz | Fastqsanger.gz | |||
| ERR9451610_1.fastq.gz | Fastqsanger.gz | |||
| ERR9451610_2.fastq.gz | Fastqsanger.gz | |||
| ERR9451620_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 152 |
Similar Datasets
Project description:BackgroundMucopolysaccharidosis IVA (Morquio syndrome A, MPS IVA) is an autosomal recessive lysosomal storage disorder caused due to biallelic variants in the N-acetylgalactoseamine-6-sulfate sulfatase (GALNS) gene. The mutation spectrum in this condition is determined amongst sub-populations belonging to the north, south and east India geography, however, sub-populations of west Indian origin, especially Gujarati-Indians, are yet to be studied. We aimed to analyse the variants present in the GLANS gene amongst the population of Gujarat by sequencing all exons and exon-intron boundaries of the GALNS gene in patients from 23 unrelated families.ResultsWe report 11 variants that include eight missense variants: (p.L36R, p.D39G, p.P77R, p.C79R, pP125L, p.P151L, p.G255A and p.L350P), one splice site variant: (c.121-7C > G), one small insertion: (c.1241_1242insA, p.I416HfsTer2) and one small deletion: (c.839_841delACA). Of these, three missense variants (p.D39G, p.G255A and p.L350P), one splice site and the two indels mentioned above are novel. Interestingly, we observed a higher than anticipated prevalence of p.P77R variant in our cohort (n = 14/25, 56%). Haplotype analysis in cases with p.P77R variant and 63 ethnicity matched healthy population controls suggested a 4 SNP haplotype block present in cases compared to controls (likelihood ratio test p-value = 1.16 × 10-13), thereby suggesting p.P77R variant as a founder variant in the Gujarati-Indian population. Furthermore, age of mutation analysis suggested the variant to have arisen approximately 450 years ago in the population.Conclusionp.P77R variant in the GLANS gene is likely to be a founder variant in MPS IVA patients of Gujarati-Indian ancestry and appeared approximately 450 years ago in the population. To our knowledge, this is the first variant to be posited as a founder variant in the GLANS gene in patients with MPS IVA syndrome.
| S-EPMC9210747 | biostudies-literature
Project description:Cancer is predominantly a somatic disease. A mutant allele found in cancer cell genome is considered somatic when it is absent in paired normal genome and dbSNP, the most comprehensive public SNP database. However, dbSNP inadequately represents several non-Caucasian populations including that from the Indian subcontinent, posing a limitation in cancer genomic analyses of data from these populations. We present TMC-SNPdb, as the first open source freely accessible (through ANNOVAR), flexible and upgradable SNP database from whole exome data of 62 normal samples derived from cancer patients of Indian origin, representing 114,309 unique germline variants. TMC-SNPdb is presented with a companion subtraction tool that can be executed with command line option or an easy-to-use graphical user interface (GUI) with the ability to deplete additional Indian population specific SNPs over and above that possible with dbSNP and 1000 Genomes databases. Using an institutional generated whole exome data set of 132 samples of Indian origin, we demonstrate that TMC-SNPdb reduced 42%, 33% and 28% false positive somatic events post dbSNP depletion in Indian origin tongue, gallbladder, and cervical cancer samples, respectively. Beyond cancer somatic analyses, we anticipate utility of TMC-SNPdb in several Mendelian germline diseases.
2018-06-06 | E-MTAB-4618 | biostudies-arrayexpress
Project description:RNA-seq data of founder mice pancreatic islets
2021-07-27 | GSE180364 | GEO
Project description:The alanine to valine mutation at codon 4 (A4V) of SOD1 causes a rapidly progressive dominant form of amyotrophic lateral sclerosis (ALS) with exclusively lower motor neuron disease and is responsible for 50% of SOD1 mutations associated with familial ALS in North America. This mutation is rare in Europe. The authors investigated the origin (geographic and time) of the A4V mutation.Several cohorts were genotyped: North American patients with confirmed A4V mutation (n = 54), Swedish (n = 3) and Italian (n = 6) A4V patients, patients with ALS with SOD1 non-A4V mutations (n = 66) and patients with sporadic ALS (n = 96), healthy white (n = 96), African American (n = 17), Chinese (n = 53), Amerindian (n = 11), and Hispanic (n = 12) subjects. High-throughput SNP genotyping was performed using Taqman assay in 384-well format. A novel biallelic CA repeat in exon 5 of SOD1, tightly linked to A4V, was genotyped on sequencing gels. Association statistics were estimated using Haploview. p Values less than 0.05 were considered significant. Age of A4V was estimated using a novel method based on r(2) degeneration with genetic distance and a Bayesian method incorporated in DMLE+.A single haplotype of 10 polymorphisms across a 5.86-cM region was associated with A4V (p = 3.0e-11) when white controls were used, suggesting a founder effect. The strength of association of this haplotype progressively decreased when African American, Chinese, Hispanic, and Amerindian subjects were used as controls. The associated European haplotype was different from the North American haplotype, indicating two founder effects for A4V (Amerindian and European). The estimated age of A4V with the r(2) degeneration method was 458 +/- 59 years (range 398-569) and in agreement with the Bayesian method (554-734 years with 80-90% posterior probability).North American SOD1 alanine to valine mutation at codon 4 descended from two founders (Amerindian and European) 400-500 years ago.
| S-EPMC2683645 | biostudies-literature
Project description:Founder mice islet RNA profiling
| PRJNA747994 | ENA
Project description:ATAC-seq data of founder mice pancreatic islets
2021-07-27 | GSE180363 | GEO
Project description:GNE gene-specific c.2179G>A(p.V727M) is a key alteration reported in patients with hereditary inclusion body myopathy (HIBM) and represents an ethnic founder mutation in the Indian cohort. However, the underlying role of this mutation in pathogenesis remains largely unknown. Thus, in this study, we aimed to access possible mechanisms of V727M mutation that could be leading to myopathy. We evaluated various in silico tools to predict the effect of this mutation on pathogenicity, structural or possible interactions, that could induce myopathy. Our results propose that V727M mutation could induce deleterious effects or pathogenicity and affect the stability of GNE protein. Analysis of differential genes reported in the V727 mutant case suggests that it can affect GNE protein interaction with Myc-proto-oncogene (MYC) transcription factor. Our in silico analysis also suggests a possible interaction between GNE ManNac-kinase domain with MYC protein at the C-terminal DNA-binding domain. MYC targets reported in skeletal muscles via ChIP-seq suggest that it plays a key role in regulating the expression of many genes reported differentially expressed in V727M-mutated HIBMs. We conclude that V727M mutation could alter the interaction of GNE with MYC thereby altering transcription of sialyltransferase and neuromuscular genes, thus understanding these effects could pave the way for developing effective therapies against HIBM.
| S-EPMC8593392 | biostudies-literature
Project description:Mutations in the DFNA5 gene are known to cause autosomal dominant non-syndromic hearing loss (ADNSHL). To date, five DFNA5 mutations have been reported, all of which were different in the genomic level. In this study, we ascertained a Korean family with autosomal dominant, progressive and sensorineural hearing loss and performed linkage analysis that revealed linkage to the DFNA5 locus on chromosome 7. Sequence analysis of DFNA5 identified a 3-bp deletion in intron 7 (c.991-15_991-13del) as the cause of hearing loss in this family. As the same mutation had been reported in a large Chinese family segregating DFNA5 hearing loss, we compared their DFNA5 mutation-linked haplotype with that of the Korean family. We found a conserved haplotype, suggesting that the 3-bp deletion is derived from a single origin in these families. Our observation raises the possibility that this mutation may be a common cause of autosomal dominant progressive hearing loss in East Asians.
| S-EPMC3433838 | biostudies-literature
Project description:The morphogen Indian Hedgehog plays a very important role during intestinal embryogenesis, but also maintains homeostasis of the adult gut. Intestinal Indian Hedgehog is expressed by the intestinal epithelium and signals in paracrine manner to fibroblasts in the stromal compartment. Unresolved deletion of Ihh from the intestinal epithelium leads to a severe enterocolitis. We studied the short term changes in the colon upon deletion of Ihh from the epithelial layer.
2017-08-25 | GSE103024 | GEO
Project description:We present a computational tool, FounderTracker, for discovering founder mutations in cancer, based on the detection of significantly conserved haplotypes in tumor SNP profiles. We demonstrate the relevance of the approach by identifying founder mutations in two different cancers, and we show with simulated data that FounderTracker can detect rare founder mutations with high power and negligible false discovery rate. FounderTracker is a powerful tool for discovering novel founder mutations that may explain part of the "missing" heritability in cancer. This SuperSeries is composed of the SubSeries listed below.
2012-03-23 | GSE32206 | GEO