DNA Copy Number Variation in Dogs

描述（由申请人提供）：由于其群体遗传学，狗是人类疾病的罕见的强大动物模型。最近的进展催生了狗遗传学的新时代。在这里，我们为犬遗传学工具箱添加了一个重要工具：DNA拷贝数遗传学。在正常人中，最近发现了数千个跨基因拷贝数变异体（CNV）。其中一些已被证明在疾病易感性中具有重要作用。我们将使用最先进的方法来创建第一个高分辨率的犬基因组CNV图谱。我们已经验证了这项技术，并发现了一个水平>50 kb的拷贝数变异，这与灵长类动物和啮齿类动物的报告相似。我们将从分子上定义一组高优先级的CNV，并确定它们在第二组狗中的频率。我们的工作将使品种特异性微缺失和其他CNV的识别与疾病的易感性和不同的性状。在未来的研究中，单核苷酸多态性（SNPs）与这些CNVs的连锁不平衡可以用来分型。因此，我们的资源和正在开发的犬27k SNP平台将是互补的。我们将与其他中心协调，以收集基于网络的CNV数据和地图分发。 公共卫生相关性：狗的自然疾病提供了优秀的动物模型，从中了解人类疾病。在这里，我们建议开发强大的新方法和资源，以寻找狗的疾病基因。我们希望这项工作将改善狗的医疗保健，并提高对人类疾病机制的理解。

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.