POPULATION GENETICS OF THE HLA REGION

HLA 区域的群体遗传学

基本信息

批准号：
3287879
负责人：
GLENYS J THOMSON
金额：
$ 9.25万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1989-03-31
项目状态：
已结题

项目摘要

Two population genetic features of the human histocompatibility (HLA) system make it ideally suited for the study of evolutionary forces acting on a population. These are the high level of polymorphism exhibited by many of the loci of the HLA system, and the existence of significant linkage disequilibrium (non-random association) between certain pairs of antigens at different loci. The distribution of allele frequencies at the HLA loci, and the patterns of linkage disequilibria, are consistent with selective events acting in the region. This proposal involves: 1) population data analysis of a number of very large data sets, including the Caucasian and Japanese data from the 8th (1980) and 9th (1984) International Histocompatibility Workshops, Japanese data from the All Japanese HLA Workshops of 1983 and 1985, Chinese data from Singapore, Indian data from New Delhi, extension of our previous analysis of a large Danish study to include additional HLA loci, and the data that will be available from the Third Asia Oceania Histocompatibility Workshop (Sapporo, Japan, 1986); 2) simulation of two and three locus neutrality models, including migration, bottleneck and founder effects; 3) statistical analysis of the distributional properties of population wide measures of disequilibrium and application of bootstrap and jackknife techniques to determine confidence limits of the measures; 4) deterministic analysis of selection models; 5) comparison of generated population genetic parameters under neutrality and selection models with the HLA data; 6) correlation of HLA antigen disease association patterns with linkage disequilibrium patterns, including comparison of patterns in different racial groups, to study the evolution of disease predisposing genes. The nature of selective events acting in the HLA region will be delineated, and the mechanism by which disease predisposing genes become common in a population investigated. The methods to be developed have applicability to other multigene families, marker trait associations and restriction fragment length polymorphism data, in all organisms.

人类组织相容性（HLA）的两个群体遗传特征系统使其非常适合研究进化力的作用在人口上。这些是高水平的多态性 HLA 系统的许多位点，以及重要的存在某些对之间的连锁不平衡（非随机关联）不同位点的抗原。等位基因频率分布 HLA 位点和连锁不平衡模式与在该地区发生的选择性事件。该提案涉及： 1）大量非常大的数据集的人口数据分析，包括第 8 次（1980 年）和第 9 次（1984 年）的白人和日本数据国际组织相容性研讨会，日本数据来自 All 1983年和1985年的日本HLA研讨会，来自新加坡的中国数据，来自新德里的印度数据，是我们之前对大量数据分析的延伸丹麦研究将包括额外的 HLA 基因座，以及将被纳入的数据可从第三届亚洲大洋洲组织相容性研讨会（札幌，日本，1986）； 2）二位点和三位点中性模型的模拟，包括迁移、瓶颈和创始人效应； 3）人口范围分布特征的统计分析不平衡的测度及bootstrap和jackknife的应用确定措施置信限度的技术； 4）选择模型的确定性分析； 5）中性下生成群体遗传参数的比较以及使用 HLA 数据的选择模型； 6) HLA抗原疾病关联模式与连锁的相关性不平衡模式，包括不同模式的比较种族群体，研究疾病诱发基因的进化。将描述作用于 HLA 区域的选择性事件的性质，以及疾病诱发基因在人群中变得普遍的机制人口调查。所开发的方法适用于其他多基因家族、标记性状关联和限制所有生物体中的片段长度多态性数据。