Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy

摘要: Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever (GRMD) resembles DMD both clinically pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding role(s) genetic modifiers may identify genes pathways that also modify phenotypes reveal novel therapies. Therefore, our objective this study was to affect discrete phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from colony (8 dystrophic, 8 non-dystrophic). All these were either full or half-siblings, phenotyped for 19 objective, quantitative biomarkers at ages 6 12 months. Each biomarker individually assessed. Gene expression profiles 59 possible candidate generated two types: cranial tibialis medial head gastrocnemius. SNPs significantly associated with identified on multiple chromosomes (including X chromosome). levels located near correlated values, roles as The results enhance understanding pathology represent first step toward characterization be relevant pathology. Such are likely useful treatment development based their relationships