Complex disease and phenotype mapping in the domestic dog.
Complex disease and phenotype mapping in the domestic dog.
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DOI：
10.1038/ncomms10460
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发表时间：
2016-01-22
影响因子：
16.6
通讯作者：
Boyko AR
中科院分区：
文献类型：
--
作者：
Hayward JJ;Castelhano MG;Oliveira KC;Corey E;Balkman C;Baxter TL;Casal ML;Center SA;Fang M;Garrison SJ;Kalla SE;Korniliev P;Kotlikoff MI;Moise NS;Shannon LM;Simpson KW;Sutter NB;Todhunter RJ;Boyko AR
家犬正在成为医学遗传学中越来越有价值的模式物种，特别有望促进我们对癌症和骨科疾病的理解。在这里，我们进行了迄今为止最大的犬全基因组关联研究，在180，000个标记上对4，200多只犬进行了基因分型，以加速作图工作。对于复杂的疾病，我们确定了与髋关节发育不良，肘关节发育不良，特发性癫痫，淋巴瘤，肥大细胞瘤和肉芽肿性结肠炎显着相关的基因座;对于形态学性状，我们报告了三个新的数量性状基因座，影响身体大小和一个影响皮毛长度和脱落。使用模拟研究，我们表明，适度较大的样本量和密集的标记集将足以识别大多数中到大的影响复杂的疾病位点。这种设计将使犬复杂疾病的有效映射，其中大多数具有人类同源物，使用的样本比人类研究所需的少得多。 家犬是我们了解癌症和其他疾病的重要模式生物。在这里，作者在多个品种中进行了全基因组关联研究，并确定了与几种复杂疾病和形态特征显著相关的新基因座。
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. The domestic dog is an important model organism for our understanding of cancer and other diseases. Here the authors conduct a genome-wide association study across multiple breeds and identify novel loci significantly associated with several complex diseases and morphological traits.