Natural genetic variation in the human genome

描述(申请人提供)：到目前为止，大多数关于人类遗传变异的研究都集中在单核苷酸多态(SNPs)上。这些单碱基变化在人类群体中相对常见，在整个人类基因组中已经发现了近1200万个SNPs。然而，SNP只代表了人类存在的遗传变异的一小部分。其他形式的遗传变异，如插入和缺失(INDELs)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。我们开发了新的实验方法来识别和研究这些可供选择的遗传变异形式。我们设想，包括SNPs、INDELs和转座子插入在内的自然遗传变异的综合图谱将比单独的SNP图谱更有助于识别直接影响人类特征和疾病的多态。我们对这一竞争性更新的未来目标是：(目标1)构建人类基因组中插入和缺失(Indel)变异的全面图谱，(目标2)研究人类群体中的Indel模式，(Aim 3)研究由转座遗传元件引起的Indel变异。这些研究将立即扩大我们对人类自然遗传变异的了解。我们的长期目标是将这些可选的变异形式整合到人类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.