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.

IGA缺乏症（IGAD）是人中最常见的原发性免疫缺陷，并且可能与更严重的疾病常见可变免疫缺陷（CVID）共享遗传易感性等位基因。肌无力重症（MG）是神经肌肉传播的最常见的原发性疾病。这些疾病中的每一个都有一个主要的MHC遗传成分，最近的证据表明在IGAD和MG的MHC III类区域中有重要影响。在拟议的研究中，将在500的MHC区域绘制关联信号 使用密集的SNP面板，瑞典MG和500个瑞典伊加德案例。同时，这些SNP将输入一组1500个瑞典控件。将确定关联信号并将其与作为成像联盟一部分研究的其他疾病中获得的疾病进行比较。提供了许多用于IGAD和CVID的瑞典多重家族，这些家族将用于评估单倍型结构，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样品也可用于打字。根据初始关联数据，我们将寻求通过键入其他SNP并重新列出候选基因来缩小相关段，以确定IGAD，CVID和MG的因果等位基因。在该项目的后期，我们将研究来自多种自身免疫性疾病遗传联盟（MADGC）的家庭，以确定各个联盟项目中确定的相关MHC等位基因和单倍型的患病率和分离。目前，有343个MADGC家庭可用，每个家庭中有2个或更多个患有2种或更多主要自身免疫性疾病的人（平均约为3.2个受影响的人 每个血统）。 RA，SLE，MS和自身免疫性甲状腺疾病在这些家族中很好地代表了，并且这些家族中有25种自身免疫性疾病。提出的研究将在许多层面上与财团的其他项目集成，并应显着促进我们对MHC对IGAD，CVID和MG的贡献的理解。