POPULATION GENETICS OF THE HLA REGION

HLA 区域的群体遗传学

• 批准号: 2177856
• 负责人: GLENYS J THOMSON
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2177856
• 关键词: MHC class I antigen; MHC class II antigen; alleles; biochemical evolution; ethnic group; family genetics; gene conversion; genetic disorder; genetic mapping; genetic markers; genetic models; genetic polymorphism; histocompatibility typing; human genetic material tag; human population genetics; immune response genes; immunogenetics; linkage mapping; major histocompatibility complex; mathematical model; nucleic acid sequence; polymerase chain reaction; restriction fragment length polymorphism; restriction mapping

The genes of the HLA System, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in the immune response, and influence susceptibility to over 40 diseases. Our understanding of the structure and function of MHC genes, their disease associations, and the evolutionary features of this multigene family has benefitted from recent advances in molecular biology, immunology, disease modelling and population genetics. Investigations by our group, and many others, have led to a deeper understanding of the molecular data and theoretical methods needed for the study of evolutionary and disease processes involving the genes of this highly variable, closely linked region. The specific aims of our research are to elucidate the evolutionary history of the HLA region, particularly the selective forces acting on HLA genes, and to delineate disease predisposing variants in the region. Our research methodology involves theoretical and empirical population genetic analysis of multilocus systems, for both allelic and DNA sequence data. A number of large HLA population data sets, including data on defined ethnic populations, will be available to us for analysis, as well as sequence data for HLA and MHC genes in other species. DNA sequence and frequency data will be available for HLA associated diseases. Our interests also extend to the study of non-HLA data. Our studies will include: HLA population single locus and multi-locus theory and data analysis, molecular typing of HLA class I and II genes in general and patient populations, single and multilocus analyses of MHC sequence data at the amino acid and nucleotide levels, mathematical modelling, simulation and data analysis of selection models for MHC regions, identification at the amino acid level of disease predisposing variants in the HLA region, and single and multilocus analyses of non-HLA population and sequence data. The results of our studies will contribute to inferences regarding the forces acting in natural populations, and how these contribute to the origin, maintenance and evolution of disease predisposing and protective alleles and other variants. Our studies apply generally to the mapping and characterization of the human genome and complex human genetic traits.

HLA 系统的基因，即主要组织相容性复合体 (MHC) 人类，控制参与免疫反应的多种功能， 并影响 40 多种疾病的易感性。我们的理解 MHC 基因的结构和功能、它们与疾病的关联以及 这个多基因家族的进化特征受益于最近的研究 分子生物学、免疫学、疾病建模和 群体遗传学。我们小组和其他许多人的调查表明 使人们对分子数据和理论有了更深入的了解 研究进化和疾病过程所需的方法 涉及这个高度可变、紧密相连的区域的基因。 我们研究的具体目的是阐明进化论 HLA 区域的历史，特别是作用于 HLA 的选择性力 基因，并描绘该区域的疾病易感变异。 我们的 研究方法涉及理论和实证的群体遗传 分析等位基因和 DNA 序列数据的多位点系统。一个 大量 HLA 人群数据集，包括特定种族的数据 群体，将可供我们进行分析以及序列 其他物种的 HLA 和 MHC 基因数据。 DNA序列和频率 将提供 HLA 相关疾病的数据。我们的兴趣也 扩展到非 HLA 数据的研究。 我们的研究将包括： HLA 群体单基因座和多基因座 理论和数据分析，HLA I 类和 II 类基因的分子分型 一般人群和患者人群、MHC 的单位点和多位点分析 氨基酸和核苷酸水平的序列数据，数学 MHC选择模型的建模、仿真和数据分析 区域，在易患疾病的氨基酸水平上进行鉴定 HLA 区域的变异以及非 HLA 的单位点和多位点分析 群体和序列数据。 我们的研究结果将有助于关于以下方面的推论 作用于自然群体的力量，以及这些力量如何促进 诱发性和保护性疾病的起源、维持和演变 等位基因和其他变体。 我们的研究通常适用于绘图 人类基因组和复杂的人类遗传特征的表征。