De-novo and genome-wide meta-analyses identify a risk haplotype for congenital sensorineural deafness in Dalmatian dogs
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ABSTRACT:
PROVIDER: PRJEB53145 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9792170_1.fastq.gz | Fastqsanger.gz | |||
| ERR9792170_2.fastq.gz | Fastqsanger.gz | |||
| ERR9792164_1.fastq.gz | Fastqsanger.gz | |||
| ERR9792164_2.fastq.gz | Fastqsanger.gz | |||
| ERR9792165_1.fastq.gz | Fastqsanger.gz |
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Project description:Congenital sensorineural deafness (CSD) has been reported to affect up to 30% of Dalmatian dogs world-wide and while unilaterally deaf dogs can live a close to normal life, dogs suffering bilateral deafness are frequently euthanized. Extreme-white coat patterning as encoded by the gene Melanocyte Inducing Transcription Factor (MITF) has long been postulated as the major risk factor for CSD in the Dalmatian breed. While attempts to identify causative risk variants associated with CSD have been numerous, no genome-wide association study has positively identified MITF as a risk locus for either bilateral or unilateral deafness in the Dalmatian breed to date. In this study, we identified an association with CSD on CFA20 in the vicinity of MITF within Australian Dalmatian dogs. Although not genome-wide significant, the association signal was validated by reanalysing publicly available data and merging the wider data resource with the local data to improve statistical power. The merged data, representing three major global populations of Dalmatian dogs, enabled us to identify a single, well-defined genome-wide significant risk haplotype for CSD. The haplotype was formed by three genome-wide significant associated markers (BICF2G630233852T>C, BICF2G630233861T>C, BICF2G630233888G>A) on CFA20 with 62% of bilaterally deaf dogs homozygous for the risk haplotype (CCA), while 30% of bilaterally deaf and 45% of hearing dogs carried one copy of the risk haplotype. Animals homozygous or heterozygous for the low-risk haplotype were less likely to be unilaterally deaf. While the association between the risk haplotype and deafness is incomplete, animals homozygous for the risk haplotype were 10-times more likely to be bilaterally deaf. Although the underlying causative variants are yet to be discovered, results from this study can now assist with reducing deafness in Dalmatian dogs.
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Project description:BackgroundCongenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD.MethodsCHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization.ResultsOur analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHD-causing genes.ConclusionsUltimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.
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Project description:A genome-wide association study (GWAS) was performed for 235 Dalmatian dogs using the canine Illumina high density bead chip to identify quantitative trait loci (QTL) associated with canine congenital sensorineural deafness (CCSD). Data analysis was performed for all Dalmatian dogs and in addition, separately for brown-eyed and blue-eyed dogs because of the significant influence of eye colour on CCSD in Dalmatian dogs. Mixed linear model analysis (MLM) revealed seven QTL with experiment-wide significant associations (-log10P>5.0) for CCSD in all Dalmatian dogs. Six QTL with experiment-wide significant associations for CCSD were found in brown-eyed Dalmatian dogs and in blue-eyed Dalmatian dogs, four experiment-wide significant QTL were detected. The experiment-wide CCSD-associated SNPs explained 82% of the phenotypic variance of CCSD. Five CCSD-loci on dog chromosomes (CFA) 6, 14, 27, 29 and 31 were in close vicinity of genes shown as causative for hearing loss in human and/or mouse.
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Project description:Background: Congenital deafness could be the first manifestation of a syndrome such as in Usher, Pendred, and Wolfram syndromes. Therefore, a genetic study is crucial in this deficiency to significantly improve its diagnostic efficiency, to predict the prognosis, to select the most adequate treatment required, and to anticipate the development of other associated clinical manifestations. Case presentation: We describe a young girl with bilateral congenital profound deafness, who initially received a single cochlear implant. The genetic study of her DNA using a custom-designed next-generation sequencing (NGS) panel detected a de novo pathogenic heterozygous variant in the WFS1 gene related to Wolfram-like syndrome, which is characterized by the presence of other symptoms such as optic atrophy. Due to this diagnosis, a second implant was placed after the optic atrophy onset. The speech audiometric results obtained with both implants indicate that this work successfully allows the patient to develop normal speech. Deterioration of the auditory nerves has not been observed. Conclusion: The next-generation sequencing technique allows a precise molecular diagnosis of diseases with high genetic heterogeneity, such as hereditary deafness, while this was the only symptom presented by the patient at the time of analysis. The NGS panel, in which genes responsible for both syndromic and non-syndromic hereditary deafness were included, was essential to reach the diagnosis in such a young patient. Early detection of the pathogenic variant in the WFS1 gene allowed us to anticipate the natural evolution of the disease and offer the most appropriate management to the patient.
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Project description:De novo copy number variations in cloned dogs from the same nuclear donor In this study, we aimed to identify de novo post-cloning CNV events and estimated the rate of CNV mosaicism in cloned dogs with the identical genetic background.
2013-12-17 | GSE49092 | GEO
Project description:De novo copy number variations in cloned dogs from the same nuclear donor In this study, we aimed to identify de novo post-cloning CNV events and estimated the rate of CNV mosaicism in cloned dogs with the identical genetic background. We analyzed CNVs in seven cloned dogs using the nuclear donor genome as reference by array-CGH
2013-12-17 | E-GEOD-49092 | biostudies-arrayexpress
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