copy number variants and common disorders filling the gaps and exploring complexity in genome-wide association studies拷贝数变异和常见疾病填补空白的全基因组关联研究和探索复杂性.pdfVIP

Review Copy Number Variants and Common Disorders: Filling the Gaps and Exploring Complexity in Genome-Wide Association Studies * ´ Xavier Estivill , Lluıs Armengol ABSTRACT degree of plasticity and that could play an important role in disease susceptibility. enome-wide association scans (GWASs) using single nucleotide polymorphisms (SNPs) have been What Have We Missed in Current Genome-Wide Gcompleted successfully for several common Association Studies? disorders and have detected over 30 new associations. SNPs are the markers that have been selected to do the Considering the large sample sizes and genome-wide SNP trick of uncovering the genetic determinants of complex coverage of the scans, one might have expected many of the traits and common disorders. This choice was mainly based common variants underpinning the genetic component of on their abundance (over 12 million SNPs), and their use was various disorders to have been identified by now. However, boosted by the technological development of tools for high- these studies have not evaluated the contribution of other throughput analysis of these variants. The Human Genome forms of genetic variation, such as structural variation, Project, followed by the HapMap Project [1] (http://www. mainly in the form of copy number variants (CNVs). Known /), has provided the landmark for the CNVs account for over 15% of the assembled human genome development of high-density SNP arrays to explore the sequence. Since CNVs ar