Copy number variation in the human genome

描述（由申请人提供）：遗传变异构成了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序列都有99.9%相同。个体之间存在的遗传变异被认为是造成特定疾病风险差异以及对药物、感染剂、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性（SNP）引起的，每个基因组中约有300万个SNP。最近，我们的实验室（以及迈克尔·威格勒的实验室）独立地发现了人类基因组中广泛存在的拷贝数增加和减少，包括数十万个DNA碱基对。一些已鉴定的变异体含有完整的基因，并且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，以及其导致或影响疾病易感性的潜力。该提案代表了由美国、英国和加拿大的研究人员组成的既定国际合作的美国部分。产生的所有信息将在公共数据库中提供，这将对临床和研究遗传学界有很大的用处。

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.