CVID, IGDA, MG Study

CVID、IGDA、MG 研究

• 批准号: 7032099
• 负责人: TIMOTHY W. BEHRENS
• 金额: $ 10.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032099
• 关键词: clinical research; cooperative study; family genetics; gene interaction; genetic mapping; genetic susceptibility; human genetic material tag; human subject; immunodeficiency; major histocompatibility complex; myasthenia gravis; single nucleotide polymorphism

IgA deficiency (IGAD) is the most common primary immunodeficiency in man, and likely shares genetic susceptibility alleles with the more severe disease common variable immune deficiency (CVID). Myasthenia gravis (MG) is the most common primary disorder of neuromuscular transmission. Each of these disorders has a major MHC genetic component, with recent evidence suggesting important effects in the MHC Class III region in IGAD and MG. In the proposed studies, association signals will be mapped across the MHC region in 500 Swedish MG and 500 Swedish IGAD cases using a dense panel of SNPs. In parallel, these SNPs will be typed in a large set of 1500 Swedish controls. Association signals will be identified and compared to those obtained in other diseases studied as part of the IMAGEN consortium. A number of Swedish multiplex families for IGAD and CVID are available, and these will be used to assess haplotype structure, and to examine segregation of haplotypes and SNP alleles with disease. Additional IGAD and CVID samples from Sweden and the U.S. are also available for typing. Based on the initial association data, we will seek to narrow the associated segments by typing additional SNPs and re-sequencing candidate genes, with a goal of identifying the causal allele(s) for IGAD, CVID and MG. Later in the project, we will study families from the Multiple Autoimmune Disease Genetics Consortium (MADGC) to determine the prevalence and segregation of associated MHC alleles and haplotypes identified in the various consortium projects. Currently, there are 343 MADGC families available, each containing 2 or more individuals with 2 or more major autoimmune diseases (average of about 3.2 affecteds per pedigree). RA, SLE, MS, and autoimmune thyroid disease are well represented in these families, and together there are mpre than 25 autoimmune disorders represented in these families. The studies proposed will be integrated with the other projects of the consortium at many levels, and should advance significantly our understanding of the MHC contribution to IGAD, CVID and MG.

伊加缺乏症（IGAD）是人类最常见的原发性免疫缺陷病，可能与更严重的常见可变免疫缺陷病（CVID）共享遗传易感性等位基因。重症肌无力（MG）是最常见的原发性神经肌肉传递障碍。这些疾病中的每一种都有一个主要的MHC遗传成分，最近的证据表明在IGAD和MG的MHC III类区域的重要影响。在拟议的研究中，关联信号将在500年内在整个MHC区域进行映射。 瑞典MG和500个瑞典IGAD病例使用密集的SNP组。与此同时，这些SNP将在1500个瑞典对照的大集合中进行分型。将识别关联信号，并与作为IMAGEN联盟一部分研究的其他疾病中获得的信号进行比较。瑞典的IGAD和CVID的多重家庭的数量是可用的，这些将被用来评估单倍型结构，并检查单倍型和SNP等位基因与疾病的分离。来自瑞典和美国的其他IGAD和CVID样本也可用于分型。基于最初的关联数据，我们将通过对额外的SNP进行分型和对候选基因进行重新测序来缩小相关片段，目的是确定IGAD、CVID和MG的致病等位基因。在该项目的后期，我们将研究来自多发性自身免疫疾病遗传学联盟（MADGC）的家族，以确定在各种联盟项目中鉴定的相关MHC等位基因和单倍型的患病率和分离。目前，有343个MADGC家族可用，每个家族包含2个或更多个患有2种或更多种主要自身免疫性疾病的个体（平均约3.2个受累个体）。 每个谱系）。RA、SLE、MS和自身免疫性甲状腺疾病在这些家族中有很好的代表性，并且在这些家族中总共有超过25种自身免疫性疾病。拟议的研究将在许多层面上与联合体的其他项目结合起来，并应大大增进我们对MHC对发展局、CVID和MG的贡献的理解。