CVID, IGDA, MG Study

免疫球蛋白缺乏症(IGAD)是人类最常见的原发免疫缺陷，可能与更严重的疾病常见变量免疫缺陷(CVID)具有相同的遗传易感性等位基因。重症肌无力(MG)是最常见的神经肌肉传递疾病。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类区域有重要的影响。在拟议的研究中，关联信号将在500中被映射到MHC区域 瑞典MG和500个瑞典IGAD病例使用密集的SNP小组。与此同时，这些SNP将被输入一大组1500个瑞典人的控制项。将识别关联信号，并将其与作为IMAGEN联盟一部分研究的其他疾病中获得的信号进行比较。目前已有许多用于IGAD和CVID的瑞典复合家系，这些家系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样本也可用于打字。在初始关联数据的基础上，我们将通过分型更多的SNPs和重新测序候选基因来缩小关联片段的范围，目的是识别IGAD、CVID和MG的因果等位基因(S)。在稍后的项目中，我们将研究多重自身免疫性疾病遗传学联合会(MADGC)的家系，以确定在不同的联合会项目中确定的相关MHC等位基因和单倍型的患病率和分离。目前，有343个MADGC家庭，每个家庭包含2个或更多患有2种或2种以上主要自身免疫性疾病的个人(平均约3.2名患者 每种血统)。类风湿关节炎、系统性红斑狼疮、多发性硬化症和自身免疫性甲状腺疾病在这些家系中有很好的代表性，加起来有超过25种自身免疫性疾病在这些家系中有代表性。拟议的研究将在多个层面上与该联盟的其他项目相结合，并应极大地促进我们对MHC对政府间发展局、国际开发署和MG的贡献的理解。

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.