Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Building 50, Room 5351, Bethesda, MD 20892, USA.
Mamm Genome. 2012 Feb;23(1-2):178-94. doi: 10.1007/s00335-011-9374-y. Epub 2011 Nov 22.
Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.
阿拉斯加雪橇犬是一个经过数代与纯种犬选择性杂交而形成的遗传独特的种群，旨在培育出高性能的运动员。由于选择性育种策略，雪橇犬为我们提供了一个独特的机会，可以利用混合映射技术来研究品种构成和特征选择如何影响基因组结构。我们使用混合映射来研究两种雪橇犬（短跑和长跑）的基因组中的遗传祖先，并将其与全基因组关联研究（GWAS）相结合，以鉴定与性能增强特征相关的区域。雪橇犬的基因组通过来自四个未混合品种（阿拉斯加雪橇犬、西伯利亚雪橇犬、德国短毛指针犬和俄罗斯猎狼犬）的不同贡献得到增强。对 115000 个全基因组 SNP 的主成分分析（PCA）清楚地将短跑和长跑群体分为不同的遗传群体，在长跑犬中观察到较长的连锁不平衡（LD）块（7.5-10 和 2.5-3.75 kb，分别）。此外，我们鉴定了八个具有选择性清除或关联分析基因组信号的区域，通过比较短跑和长跑犬的祖先，这些区域得到了证实。对精英和表现不佳的雪橇犬的比较确定了一个与耐热性显著相关的单一区域。在该区域内，我们在肌球蛋白重链 9 基因（MYH9）中鉴定了七个与短跑犬耐热性显著相关的 SNP，其中两个对应于人类同源物中的保守启动子和增强子区域。
