title: Genome-wide association studies for multiple diseases of the German Shepherd Dog.
abstract: The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.
authors: Department of Genetics and Biochemistry, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC 29634, USA.
authors: Kate L
authors: KL
authors: Tsai
authors: Rooksana E
authors: RE
authors: Noorai
authors: Alison N
authors: AN
authors: Starr-Moss
authors: Pascale
authors: P
authors: Quignon
authors: Caitlin J
authors: CJ
authors: Rinz
authors: Elaine A
authors: EA
authors: Ostrander
authors: Jörg M
authors: JM
authors: Steiner
authors: Keith E
authors: KE
authors: Murphy
authors: Leigh Anne
authors: LA
authors: Clark
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D004393:Dwarfism, Pituitary / Q000235:genetics / Q000662:veterinary*; D004931:Esophageal Achalasia / Q000235:genetics / Q000662:veterinary*; D020022:Genetic Predisposition to Disease; D016678:Genome; D055106:Genome-Wide Association Study / Q000662:veterinary*; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D010182:Pancreatic Diseases / Q000235:genetics / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide; D013118:Spinal Cord Diseases / Q000235:genetics / Q000662:veterinary*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D014157:Transcription Factors; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1