Distribution and functional impact of DNA copy number variation in the rat
Distribution and functional impact of DNA copy number variation in the rat
复制标题
DOI：
10.1038/ng.141
复制
发表时间：
2008-05-01
期刊：
影响因子：
30.8
通讯作者：
Cuppen, Edwin
中科院分区：
文献类型：
--
作者：
Guryev, Victor;Saar, Kathrin;Cuppen, Edwin
哺乳动物基因组中拷贝数变异体（CNVs）的丰度和动态对确定其对自然和疾病表型的影响提出了新的挑战。我们使用计算和实验方法对大鼠的CNVs进行分类，发现它们与人类的CNVs具有重要的功能特征。此外，在人类和大鼠中，113个一对一的正向同源基因与CNV重叠，其中80个与人类疾病有关。CNV在整个基因组中是非随机分布的。18号染色体是CNV的冷点，也是进化重排和片段复制的冷点，表明CNV发生或维持的严格选择机制。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的CNVs的功能关系。这些特征使大鼠成为研究结构变异与人类复杂性状和疾病相关的表型效应的极好模型。
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.