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（domestic dog）正日益成为医学遗传学领域极具价值的模式物种，在推动我们对癌症与骨科疾病的认知方面展现出尤为可观的应用前景。本研究开展了迄今为止规模最大的犬全基因组关联研究，采用包含4200余只受试犬的基因分型队列，对18万个遗传标记进行了基因分型，以加速致病位点的定位工作。针对复杂疾病，我们鉴定出与髋关节发育不良、肘关节发育不良、特发性癫痫、淋巴瘤、肥大细胞瘤及肉芽肿性结肠炎显著相关的遗传位点；针对形态学性状，本研究报道了3个影响犬只体型的全新数量性状位点（quantitative trait loci），以及1个调控被毛长度与脱毛程度的数量性状位点。通过模拟研究，我们证实，适度扩大样本规模并提升遗传标记密度，即可鉴定出绝大多数中等到大效应的复杂疾病相关位点。该研究方案可实现犬复杂疾病的高效定位——此类疾病大多存在人类同源疾病对应体——且所需样本量远低于人类同类研究的样本需求。