Data from: Complex disease and phenotype mapping in the domestic dog

The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.家犬在医学遗传学领域正成为愈发重要的模式物种，在增进我们对癌症与骨科疾病的认知方面展现出突出潜力。本研究开展了迄今为止规模最大的犬全基因组关联研究（genome-wide association study），依托由4200余只犬组成、经18万个遗传标记完成基因分型的研究队列，以加速疾病相关遗传位点的定位工作。针对复杂疾病，我们鉴定出与髋关节发育不良（hip dysplasia）、肘关节发育不良（elbow dysplasia）、特发性癫痫（idiopathic epilepsy）、淋巴瘤、肥大细胞瘤（mast cell tumour）及肉芽肿性结肠炎（granulomatous colitis）显著相关的遗传基因座；针对形态性状，我们报道了3个全新的、可影响体型的数量性状基因座（quantitative trait loci），以及1个可影响被毛长度与脱毛程度的基因座。通过模拟研究，我们证实，仅需适度扩大样本量并提升遗传标记密度，即可鉴定出绝大多数具有中等到大效应的复杂疾病基因座。该研究提出的实验设计，能够以远低于人类研究所需的样本量，高效定位绝大多数拥有人类同源疾病的犬类复杂疾病遗传位点。