Natural genetic variation in the human genome

人类基因组的自然遗传变异

• 批准号: 7117405
• 负责人: Scott E Devine
• 金额: $ 29.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117405
• 关键词: animal tissue; biochemical evolution; cell line; computer assisted sequence analysis; data quality /integrity; gene deletion mutation; gene expression; gene mutation; genetic mapping; genetic polymorphism; genetic screening; human genetic material tag; human population genetics; human tissue; nucleic acid sequence; polymerase chain reaction; single nucleotide polymorphism; transposon /insertion element

DESCRIPTION (provided by applicant): We have developed a computational pipeline to identify DNA sequence variations in the human genome. The pipeline uses the shotgun sequencing data that were generated by the SNP Consortium from 24 diverse humans (Nature 409, 928-933). Our preliminary data indicate that this collection of approximately 7.1 million shotgun sequencing reads is a rich resource for discovering a wide range of DNA polymorphisms in humans, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs) and transposon polymorphisms. The major goal of this proposal is to use our pipeline to identify additional DNA sequence variations and then perform verification experiments to measure the accuracy of our predictions. We will focus most of our efforts on identifying INDEL polymorphisms in humans. We also will identify and study the subclass of INDELs that are caused by de novo transposon insertions in humans. Such elements represent a source of human variation, and, as endogenous mutagens, may also be responsible for generating mutations that lead to human diseases. Finally, we will use our methods to identify INDELs that have occurred in the chimp genome relative to the human genome. Such INDELs will help us to identify additional forms of mobile DNA in chimps and humans, and also may provide insights on the genetic events leading to the speciation of these organisms.

描述（由申请人提供）： 我们开发了一个计算管道来识别人类基因组中的 DNA 序列变异。该管道使用 SNP 联盟从 24 名不同人类 (Nature 409, 928-933) 生成的鸟枪法测序数据。我们的初步数据表明，大约 710 万条鸟枪法测序读数的集合是发现人类广泛 DNA 多态性的丰富资源，包括单核苷酸多态性 (SNP)、插入/删除多态性 (INDEL) 和转座子多态性。该提案的主要目标是使用我们的管道来识别额外的 DNA 序列变异，然后进行验证实验来衡量我们预测的准确性。我们将把大部分精力集中在识别人类的 INDEL 多态性上。我们还将鉴定和研究由人类从头插入转座子引起的 INDEL 亚类。这些元件代表了人类变异的来源，并且作为内源性诱变剂，也可能导致产生导致人类疾病的突变。最后，我们将使用我们的方法来识别黑猩猩基因组中相对于人类基因组发生的 INDEL。此类 INDEL 将帮助我们识别黑猩猩和人类中其他形式的可移动 DNA，并且还可能提供有关导致这些生物体物种形成的遗传事件的见解。