Identification of genetic susceptibility factors associated with canine gastric dilatation-volvulus
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ABSTRACT:
PROVIDER: PRJNA592193 | ENA |
REPOSITORIES: ENA
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Project description:Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. GDV is a complex disease with risk factors including age, diet, behavior, family history, and genetics. The genetic correlates of GDV have not previously been systematically explored. We undertook multiplatform genome-wide association analysis (GWAS) of 253 dogs including 106 healthy dogs and 147 dogs with at least one GDV episode. The study included ten dog breeds enriched for Borzoi, German Shepherd (GSD), Great Dane, and Standard Poodle. SNP array genotyping was performed on constitutional DNA from all 241 samples to identify GDV-associated SNPs and CNVs. To increase the coverage of our study we performed imputation analysis of the SNP data as well as additional whole genome sequencing (WGS) on a subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds). Twenty-one patients were genotyped by both SNP and WGS platforms. The GWAS was conducted across breeds as well as on specific breeds using a mixed linear model adjusting for relatedness, population structure and sex. After genome-wide Bonferroni correction, we identified a significant protective GDV-associated SNP, rs851737064, occurring in an intergenic region, across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 additional independent, protective and deleterious SNPs with significant GDV association. Additional GWAS conducted on Borzoi, GSD and Great Dane yielded significant genome-wide GDV associations in 11 independent SNPs, while that in Borzoi alone identified 2 independent GDV-associated SNPs. We then used WGS data to validate the imputation analysis. Notable significant SNPs included genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. From the WGS data we also detected two independent GDV-associated SNPs in Borzoi, GSD and Great Dane breeds on an intergenic region on chromosome 7 not covered by previous analyses. These data provide important new information regarding canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
2020-12-01 | GSE141128 | GEO
Project description:Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. The genetic correlates of GDV have not previously been systematically explored. We undertook an inter-breed genome-wide association analysis (GWAS) of 253 dogs from ten breeds including 106 healthy dogs and 147 dogs with at least one GDV episode. SNP array genotyping followed by imputation was conducted on 241 samples to identify GDV-associated single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs). A subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds) was characterized by whole genome sequencing (WGS). After genome-wide Bonferroni correction, we identified a significant putatively protective intergenic SNP (rs851737064) across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 significant additional putatively protective or deleterious SNPs. Notable significant SNPs included those occurring in genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. These data provide important new clues to canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
| S-EPMC7694454 | biostudies-literature
Project description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ Onchocerca volvulus is a filarial nematode parasite of humans, causing Onchocerciasis, or River Blindness, which affects over 37 million people, mainly in Africa. It is a severely debilitating disease, which is transmitted to humans by black fly. This project aims to undertake high-throughput sequencing of Onchocerca volvulus transcriptome for de novo assembly of transcripts. The main objective of this project is to recognize genes expressed in given life stages.
2013-01-28 | E-ERAD-67 | biostudies-arrayexpress
Project description:Stage-specific proteomes of Onchocerca volvulus and its endosymbiont Wolbachia
2016-11-21 | PXD003585 | Pride
Project description:Onchocerca volvulus poolSeq from 20 female worms from Ecuador
| PRJNA336187 | ENA
Project description:Onchocerca volvulus genome sequencing project
| PRJNA37761 | ENA
Project description:Well-defined, closed breeding populations coupled with excessive disease predispositions among purebred domestic dog breeds offer unique advantages to genetic studies of disease susceptibility. Advantages offered by canine population substructure, combined with similarity to human disease in terms of clinical presentation and response to treatment, make the dog a particularly attractive system for finding genes associated with cancer. Cancers that have been difficult to study in human families or populations are of particular interest, especially those associated with one or a small number of breeds and a high level of occurrence. Histiocytic sarcoma (HS) is a rare and poorly understood neoplasm in humans, however it occurs in 15-25% of Bernese Mountain Dogs (BMD). By combining genome-wide association studies from two geographic populations of BMD followed by fine mapping and sequencing, we have identified a cancer-associated haplotype within the MTAP/CDKN2A locus that is present in 95% of all affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in numerous complex genetic diseases including several cancers. These results demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and yet poorly understood genomic region. Genomic DNA was collected from affected and unaffected BMD in North America (NA) and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci.
2012-07-02 | E-GEOD-38011 | biostudies-arrayexpress
Project description:Well-defined, closed breeding populations coupled with excessive disease predispositions among purebred domestic dog breeds offer unique advantages to genetic studies of disease susceptibility. Advantages offered by canine population substructure, combined with similarity to human disease in terms of clinical presentation and response to treatment, make the dog a particularly attractive system for finding genes associated with cancer. Cancers that have been difficult to study in human families or populations are of particular interest, especially those associated with one or a small number of breeds and a high level of occurrence. Histiocytic sarcoma (HS) is a rare and poorly understood neoplasm in humans, however it occurs in 15-25% of Bernese Mountain Dogs (BMD). By combining genome-wide association studies from two geographic populations of BMD followed by fine mapping and sequencing, we have identified a cancer-associated haplotype within the MTAP/CDKN2A locus that is present in 95% of all affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in numerous complex genetic diseases including several cancers. These results demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and yet poorly understood genomic region.
2012-07-03 | GSE38011 | GEO