Mapping DNA structural variation in dogs
Mapping DNA structural variation in dogs
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DOI：
10.1101/gr.083741.108
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发表时间：
2009-03-01
期刊：
影响因子：
7
通讯作者：
Alvarez, Carlos E.
中科院分区：
文献类型：
--
作者：
Chen, Wei-Kang;Swartz, Joshua D.;Alvarez, Carlos E.
DNA结构变异（SV）是遗传多样性的重要组成部分，但其生物学影响尚不清楚。我们认为，狗的遗传历史和非凡的表型变异使它们成为研究SV对生物学和疾病影响的理想哺乳动物。现存的数百种狗是通过选择极端的形态和行为特征而产生的。除了这些特征，每个品种患不同疾病的风险都会增加。我们使用阵列CGH创建了狗的DNA拷贝数变异（CNV）或SV的第一张地图。这种变异的程度，以及一些受影响的基因类别，与小鼠和人类相似。大多数犬类CNVs影响基因，包括疾病和候选疾病基因，因此可能是功能性的。我们发现了许多可能是品种或品种类别特定的CNVs。CNV区域聚类分析表明，犬种倾向于按品种分类分组。我们的综合研究结果表明，许多CNVs(1)与侧翼序列存在连锁不平衡，(2)与品种特异性性状相关。我们讨论了狗的结构变异目录将如何加速犬性状和疾病的遗传基础的鉴定，从使用全基因组关联和候选cnv /基因方法开始。
DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH to create the first map of DNA copy number variation (CNV) or SV in dogs. The extent of this variation, and some of the gene classes affected, are similar to those of mice and humans. Most canine CNVs affect genes, including disease and candidate disease genes, and are thus likely to be functional. We identified many CNVs that may be breed or breed class specific. Cluster analysis of CNV regions showed that dog breeds tend to group according to breed classes. Our combined findings suggest many CNVs are (1) in linkage disequilibrium with flanking sequence, and (2) associated with breed-specific traits. We discuss how a catalog of structural variation in dogs will accelerate the identification of the genetic basis of canine traits and diseases, beginning with the use of whole genome association and candidate-CNV/gene approaches.