Copy number variation in the human genome

描述(申请人提供)：基因变异是进化和人类多样性的基础。来自人类基因组计划的数据最初表明，任何两个人的DNA序列都是99.9%相同的。个体之间存在的遗传差异被认为是特定疾病风险的差异以及对药物、传染病、毒素和环境因素的不同反应的原因。直到最近，大多数人类遗传变异似乎都是由单核苷酸多态(SNPs)引起的，每个个体基因组中约有300万个SNPs。最近，我们的实验室(和Michael Wigler的实验室)独立发现了人类基因组中广泛存在的拷贝数增减，包括数十万个DNA碱基对。一些已识别的变异体包含完整的基因，在某些情况下与已知的疾病基因座重叠。在这项研究中，我们将使用最先进的、跨平台的基因组技术来更好地表征这种新发现的变异类型的程度和频率，以及它导致或影响疾病易感性的可能性。这项提案代表了美国与来自美国、英国和加拿大的调查人员已建立的国际合作的组成部分。所有产生的信息将在公共数据库中提供，这些数据库将对临床和研究遗传学社区具有巨大的实用价值。

DESCRIPTION (provided by applicant): Genetic variation forms the basis of evolution and human diversity. Data from the Human Genome Project originally suggested that any two humans are 99.9% identical in their DNA sequences. The genetic variation that exists between individuals is thought to account for differences in risks to specific diseases as well as differential responses to drugs, infectious agents, toxins, and environmental factors. Until recently, most human genetic variation appeared to be accounted for by single-nucleotide polymorphisms (SNPs), constituting some three million SNPs in each individual genome. Recently, our laboratory (and that of Michael Wigler's) independently discovered the wide-spread existence of copy number gains and losses in the human genome, encompassing hundreds of thousands of basepairs of DNA. Some of the identified variants contain entire genes, and in some cases overlap with known disease loci. In this study, we will use state-of-the-art, cross-platform genomic technologies to better characterize the extent and frequency of this newly discovered type of variation, and its potential to cause or influence susceptibility to disease. This proposal represents the US component of an established international collaboration involving investigators from the US, United Kingdom and Canada. All information generated will be made available in public databases that will have great utility for the clinical and research genetics community.