DNA Copy Number Variation in Dogs

描述（由申请人提供）：很大程度上由于它们的种群遗传学，狗是罕见的强大的人类疾病动物模型。最近的进展开创了狗遗传学的新时代。在这里，我们增加了一个重要的工具，犬遗传学工具箱：DNA拷贝数遗传学。在正常人中，最近发现了数千种基因跨越拷贝数变异（CNVs）。其中一些已被证明在疾病易感性中起着重要作用。我们将使用最先进的方法来创建狗基因组的第一个高分辨率CNV图。我们对该技术进行了验证，并发现了与灵长类动物和啮齿动物相似的bbb50 kb拷贝数变异水平。我们将从分子上定义一组高优先级的CNVs，并在第二组狗中确定它们的频率。我们的工作将使鉴定品种特异性微缺失和其他与疾病易感性和多种性状相关的CNVs成为可能。在未来的研究中，与这些CNVs连锁不平衡的单核苷酸多态性（SNPs）可以用来对它们进行基因分型。因此，我们的资源和正在开发的犬类27k SNP平台将是互补的。我们将与其他中心合作，整合基于网络的CNV数据和地图分布。

DESCRIPTION (provided by applicant): Largely due to their population genetics, dogs are uncommonly powerful animal models of human disease. Recent advances have spawned a new era of dog genetics. Here we add an important tool to the canine genetics toolbox: DNA copy number genetics. In normal humans, thousands of gene-spanning Copy Number Variants (CNVs) were recently identified. Some of these have been shown to have strong roles in disease predisposition. We will use state of the art methods to create the first high resolution CNV map of the dog genome. We have validated the technology and find a level of >50 kb copy number variation that is similar to that reported for primates and rodents. We will molecularly define a high-priority set of CNVs and determine their frequencies in a second panel of dogs. Our work will enable the identification of breed-specific microdeletions and other CNVs that are associated with disease susceptibility and diverse traits. In future studies Single Nucleotide Polymorphisms (SNPs) in linkage disequilibrium with these CNVs can be used to genotype them. Thus our resource and the canine 27k SNP platforms under development will be complementary. We will co-ordinate with other centers to assemble web based distribution of CNV data and maps. PUBLIC HEALTH RELEVANCE: Natural diseases of dogs offer outstanding animal models from which to learn about human disease. Here we propose to develop powerful new approaches and resources for finding dog disease genes. We expect this work will lead to improved health care in dogs, and to the improved understanding of human disease mechanisms.