Copy number variation in the human genome

描述（由申请人提供）：遗传变异是进化和人类多样性的基础。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变异被认为可以解释特定疾病风险的差异，以及对药物、传染因子、毒素和环境因素的不同反应。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（SNPs）来解释的，每个个体基因组中大约有300万个snp。最近，我们的实验室（以及Michael Wigler的实验室）独立地发现，人类基因组中拷贝数的增加和减少广泛存在，包括数十万个DNA碱基对。一些已确定的变异包含整个基因，在某些情况下与已知的疾病位点重叠。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范围和频率，以及它引起或影响疾病易感性的潜力。该提案代表了美国、英国和加拿大调查员参与的既定国际合作的美国组成部分。所有产生的信息将在公共数据库中提供，这将对临床和研究遗传学社区有很大的效用。

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.