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）： 我们已经开发了一种计算管道来识别人类基因组中的DNA序列变化。该管道使用SNP联盟从24种不同人类产生的shot弹枪测序数据（自然409，928-933）。我们的初步数据表明，大约710万张shot弹枪测序读数的集合是发现人类中广泛的DNA多态性的丰富资源，包括单核苷酸多态性（SNP），插入/缺失/缺失多态性（INDELS）和转子多态性多态性。该提案的主要目标是使用我们的管道来识别其他DNA序列变化，然后执行验证实验以衡量我们的预测的准确性。我们将重点放在确定人类中的indel多态性上。我们还将识别和研究由人类从头转座子插入引起的indels的子类。这样的元素代表了人类变异的根源，作为内源性诱变剂，也可能负责产生导致人类疾病的突变。最后，我们将使用我们的方法来鉴定科姆基因组相对于人类基因组中发生的插入。这样的印度将帮助我们确定黑猩猩和人类中的其他形式的移动DNA，也可能会提供有关导致这些生物物种形成的遗传事件的见解。