MODELS IN POPULATION GENETICS

群体遗传学模型

• 批准号: 2685132
• 负责人: GLENYS J THOMSON
• 金额: $ 17.22万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685132
• 关键词: European; Hodgkin's disease; MHC class I antigen; MHC class II antigen; T cell receptor; alleles; antiserum; artificial intelligence; biochemical evolution; celiac disease; computer assisted sequence analysis; computer data analysis; disease /disorder proneness /risk; gene frequency; genetic counseling; genetic disorder diagnosis; genetic markers; genetic models; genetic polymorphism; genotype; hereditary hemochromatosis; heterozygote; histocompatibility antigens; histocompatibility gene; homozygote; human genetic material tag; human population genetics; immunogenetics; insulin dependent diabetes mellitus; linkage disequilibriums; mathematical model; molecular genetics; multiple sclerosis; nucleic acid sequence; oligonucleotides; restriction fragment length polymorphism; rheumatoid arthritis; serotyping; statistics /biometry

The genes of the human leukocyte antigen (HLA) region 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 the HLA 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. Theoretical studies in the development of models to determine the modes of inheritance of the HLA associated diseases have led to a better understanding of the inheritance patterns in insulin dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic components. The specific aims of our research are to study the genetic components in the etiology of the HLA associated diseases, and population genetic features of the HLA system. A variety of methods to test modes of inheritance of diseases using marker allele information, will be developed. Methods appropriate for the analysis of marker systems which are not highly polymorphic, to both detect linkage and determine modes of inheritance, will be investigated. The information content of particular pedigree types for LOD score analysis will be investigated. Two methods using patterns of linkage disequilibrium will be investigated to determine their usefulness in mapping disease predisposing genes. A number of large collaborative data sets of HLA associated diseases will be analyzed. A framework for genetic counselling of HLA associated, and other complex diseases, will be developed. The results of our studies are generally applicable to the mapping and characterization of complex human genetic traits.

人类白细胞抗原（HLA）区域的基因控制着多种 参与免疫反应的功能及其影响 易患 40 多种疾病。 我们对结构的理解 HLA 基因的功能和功能、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。 模型开发的理论研究 确定HLA相关疾病的遗传模式 有助于更好地了解胰岛素的遗传模式 依赖性糖尿病、类风湿性关节炎、多发性硬化症、 强直性脊柱炎、血色素沉着病、乳糜泻等。 它 现在已经清楚，许多 HLA 相关疾病涉及 HLA 成分以及非 HLA 遗传的异质性 成分。 我们研究的具体目标是研究遗传成分 HLA相关疾病的病因学和群体遗传 HLA系统的特点 多种测试模式的方法 使用标记等位基因信息进行疾病遗传，将 发达。 适用于分析标记系统的方法 不具有高度多态性，无法检测连锁并确定连锁模式 继承，将被调查。 具体的信息内容 将调查 LOD 评分分析的谱系类型。 两种方法 将研究使用连锁不平衡模式 确定它们在绘制疾病易感基因图谱中的有用性。 一个 HLA 相关疾病的大量协作数据集将 进行分析。 HLA 相关遗传咨询框架，以及 将会发展出其他复杂的疾病。 我们的研究结果 通常适用于复杂的映射和表征 人类遗传特征。