LINKAGE DISEQUILIBRIUM IN THE HUMAN GENOME

人类基因组中的连锁不平衡

• 批准号: 2861487
• 负责人: Anna Di Rienzo
• 金额: $ 36.44万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2861487
• 关键词: African; Asians; European; Italy; blood groups; computer simulation; electron microscopy; ethnic group; evolution; gene expression; genetic mapping; genetic polymorphism; genome; haploidy; high performance liquid chromatography; human genetic material tag; human population composition; human population genetics; human population growth; human subject; linkage disequilibriums; molecular cloning; natural selections; nucleic acid sequence; nucleotides; polymerase chain reaction

DESCRIPTION (Adapted from the Investigator's Abstract): The main goal of this proposal is to elucidate how demography and natural selection have shaped the organization of sequence variation and linkage disequilibrium (LD) in the human genome and across human populations. Such an understanding will provide critical background information needed to design studies aimed at dissecting the genetic bases of complex phenotypes. To advance these goals, the investigators propose the following specific aims: 1. To survey sequence variation and LD in three ethnically diverse populations at up to ten pairs of tightly, but not completely linked loci to: a) evaluate the effect of different demographic scenarios on patterns of variation and LD; b) estimate the parameters of the inferred demographic model for human populations; and c) develop expectations for the amount and inter-locus variability of sequence variation and LD at the genome-wide level by computer simulations. For each locus 1-2 kb of sequence will be surveyed for variation in samples of 30-50 chromosomes from three large populations representative of the major ethnic groups: Cameroon (Africa), Han Chinese (Asia) and Italians (Europe). The investigators have already shown by computer simulations that this is a highly efficient and informative approach to develop expectations for the pattern of variation and LD at the genome-wide level. In addition they will be able to characterize how genetic variation and LD is organized across major ethnic groups. 2. The investigators will survey sequence variation and reconstruct haplotypes around two common variants: G6PDdef and Duffy O blood group (FY). These are known to have evolved under positive selection in African populations. In particular, they will estimate nucleotide diversity and LD in the regions flanking the site under selection and compare these quantities in neutrally evolving regions. This analysis is aimed at characterizing the signature of selection on the pattern of LD and sequence variation linked to the variants examined.

描述（改编自研究者摘要）：本提案的主要目标是阐明人口统计学和自然选择如何在人类基因组和人群中形成序列变异和连锁不平衡（LD）的组织。这样的理解将为设计旨在剖析复杂表型的遗传基础的研究提供关键的背景信息。为了推进这些目标，研究者提出了以下具体目标：1。在3个不同种族的人群中，对多达10对紧密相连但不完全相连的基因座进行序列变异和LD调查，以达到以下目的：a)评估不同人口情景对变异模式和LD的影响；B)估计推断的人口统计模型的参数；c)通过计算机模拟对序列变异和LD在全基因组水平上的数量和位点间变异性进行预测。对于每个基因座1-2 kb的序列，将在30-50个染色体样本中进行调查，这些样本来自三个具有代表性的主要族群：喀麦隆（非洲）、汉人（亚洲）和意大利人（欧洲）。研究人员已经通过计算机模拟表明，这是一种高效和信息丰富的方法，可以在全基因组水平上对变异模式和LD进行预期。此外，他们将能够描述遗传变异和LD是如何在主要种族群体中组织的。2. 研究人员将调查序列变异并重建两种常见变异的单倍型：G6PDdef和Duffy O血型（FY）。已知这些是在非洲人口的积极选择下进化而来的。特别是，他们将估计选择位点两侧区域的核苷酸多样性和LD，并在中性进化区域比较这些数量。这一分析的目的是表征选择的特征在模式的LD和序列变异连接到变异检查。