Copy-number variation and association studies of human disease
Copy-number variation and association studies of human disease
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DOI：
10.1038/ng2080
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发表时间：
2007-07-01
期刊：
影响因子：
30.8
通讯作者：
Altshuler, David M.
中科院分区：
文献类型：
--
作者：
McCarroll, Steven A.;Altshuler, David M.
人类遗传学的中心目标是了解人类表型变异的遗传基础，阐明人类生理学、进化和疾病。在两千种孟德尔疾病中发现了罕见的突变；最近，系统地评估共同snp对复杂疾病的贡献已经成为可能。拷贝数改变在散发性基因组疾病中的已知作用，结合有关遗传拷贝数变异的新信息，表明系统评估拷贝数变异（CNVs）的重要性，包括常见拷贝数多态性（CNPs）。在这里，我们讨论了CNVs影响表型的证据，支持CNVs临床研究的基础知识方向，CNPs在临床队列中基因分型的挑战，SNPs作为CNPs标记的使用以及CNVs与疾病相关性测试的统计挑战。关键的需求是常见CNPs的高分辨率地图和准确确定受影响个体等位基因状态的技术。
The central goal of human genetics is to understand the inherited basis of human variation in phenotypes, elucidating human physiology, evolution and disease. Rare mutations have been found underlying two thousand mendelian diseases; more recently, it has become possible to assess systematically the contribution of common SNPs to complex disease. The known role of copy-number alterations in sporadic genomic disorders, combined with emerging information about inherited copy-number variation, indicate the importance of systematically assessing copy-number variants (CNVs), including common copy-number polymorphisms (CNPs), in disease. Here we discuss evidence that CNVs affect phenotypes, directions for basic knowledge to support clinical study of CNVs, the challenge of genotyping CNPs in clinical cohorts, the use of SNPs as markers for CNPs and statistical challenges in testing CNVs for association with disease. Critical needs are high-resolution maps of common CNPs and techniques that accurately determine the allelic state of affected individuals.