Natural genetic variation in the human genome

描述（由申请人提供）：迄今为止对人类遗传变异进行的大多数研究都集中在单核苷酸多态性（SNP）上。这些单碱基变化在人群中相对常见，并且在整个人类基因组的位点上已经鉴定出近1200万个SNP。然而，SNPs仅代表人类遗传变异的一小部分。替代形式的遗传变异，如插入和缺失（INDEL）和转座子插入在人类中也很丰富，但这些形式的遗传变异仍然相对未被探索。我们已经开发了新的实验方法来识别和研究这些替代形式的遗传变异。我们设想，包括SNP、INDEL和转座子插入的自然遗传变异的综合图谱将比单独的SNP图谱更有用，用于鉴定直接影响人类性状和疾病的多态性。我们未来的目标是：（目的1）构建一个全面的插入和缺失（INDEL）在人类基因组中的变化，（目的2）研究INDEL模式在人类种群和（目的3）研究INDEL变异，是由转座遗传因子。这些研究将立即扩大我们对人类自然遗传变异的认识。我们的长期目标是将这些变异的替代形式整合到人类HapMap中，并研究这些变异对人类表型和疾病的影响。

DESCRIPTION (provided by applicant): Most studies that have been conducted thus far with human genetic variation have been focused on single nucleotide polymorphisms (SNPs). These single base changes are relatively common in human populations, and almost 12 million SNPs have been identified at sites throughout the human genome. However, SNPs represent only a fraction of the genetic variation that exists in humans. Alternative forms of genetic variation, such as insertions and deletions (INDELs) and transposon insertions also are abundant in humans, yet these forms of genetic variation remain relatively unexplored. We have developed new experimental approaches to identify and study these alternative forms of genetic variation. We envision that integrated maps of natural genetic variation that include SNPs, INDELs, and transposon insertions will be more useful than SNP maps alone for identifying polymorphisms that directly influence human traits and diseases. Our future goals with this competitive renewal are to: (Aim 1) construct a comprehensive map of insertion and deletion (INDEL) variation in the human genome, (Aim 2) study INDEL patterns in human populations and (Aim 3) study INDEL variation that is caused by transposable genetic elements. These studies will immediately expand our knowledge of natural genetic variation in humans. Our long-term goal is to integrate these alternative forms of variation into the human HapMap and to study the impact of these variants on human phenotypes and diseases.