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家犬复杂疾病与表型定位

Complex disease and phenotype mapping in the domestic dog.

作者信息

Hayward Jessica J, Castelhano Marta G, Oliveira Kyle C, Corey Elizabeth, Balkman Cheryl, Baxter Tara L, Casal Margret L, Center Sharon A, Fang Meiying, Garrison Susan J, Kalla Sara E, Korniliev Pavel, Kotlikoff Michael I, Moise N S, Shannon Laura M, Simpson Kenneth W, Sutter Nathan B, Todhunter Rory J, Boyko Adam R

机构信息

Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.

出版信息

Nat Commun. 2016 Jan 22;7:10460. doi: 10.1038/ncomms10460.

Abstract

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.

摘要

家犬正日益成为医学遗传学中一个极具价值的模式物种,在推动我们对癌症和骨科疾病的理解方面展现出特别的前景。在此,我们开展了迄今为止最大规模的犬类全基因组关联研究,对4200多只犬进行了18万个标记的基因分型,以加速定位工作。对于复杂疾病,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著相关的基因座;对于形态特征,我们报告了三个影响体型的新数量性状基因座和一个影响毛长及脱毛的基因座。通过模拟研究,我们表明适度增加样本量和使用更密集的标记集足以识别大多数中等到大效应的复杂疾病基因座。这种提议的设计将能够高效定位犬类复杂疾病,其中大多数疾病在人类中有同源物,且所需样本量远少于人类研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f019/4735900/d5f43c829321/ncomms10460-f1.jpg

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