Guryev Victor, Saar Kathrin, Adamovic Tatjana, Verheul Mark, van Heesch Sebastiaan A A C, Cook Stuart, Pravenec Michal, Aitman Timothy, Jacob Howard, Shull James D, Hubner Norbert, Cuppen Edwin
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Nat Genet. 2008 May;40(5):538-45. doi: 10.1038/ng.141.
The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.
哺乳动物基因组中拷贝数变异（CNV）的丰度和动态变化，给鉴定其对自然表型和疾病表型的影响带来了新的挑战。我们运用计算和实验方法对大鼠的CNV进行编目，发现它们与人类的CNV具有重要的功能特征。此外，113个直系同源基因在人类和大鼠的CNV中重叠，其中80个与人类疾病有关。CNV在整个基因组中呈非随机分布。18号染色体是CNV以及进化重排和节段性重复的冷区，这表明CNV发生或维持背后存在严格的选择机制。通过利用大鼠重组近交系的基因表达数据，我们建立了22个表达数量性状位点（eQTL）背后的CNV的功能关系。这些特征使大鼠成为研究与人类复杂性状和疾病相关的结构变异的表型效应的优秀模型。
