Fine-mapping Association Analysis of Total IgE on Chr. 20p12 in Costa Ricans

描述（由申请人提供）： 虽然哮喘是一个重要的公共卫生问题，在西班牙裔美国人在美国和拉丁美洲，很少有人知道遗传因素的贡献，哮喘的发病机制，在这个种族群体。我们以前已经确定了显着的证据连锁总血清IgE染色体20 p12之间的男性在遗传隔离的西班牙裔人口在哥斯达黎加。该建议旨在确定染色体20p12上总血清IgE（哮喘的关键中间表型）的遗传决定因素。我们将首先对哥斯达黎加哮喘男孩及其父母染色体20p12上的血清总IgE进行精细映射关联分析。然后，我们将尝试在儿童哮喘管理项目（CAMP）中的白色（非西班牙裔）男孩家庭中复制阳性结果。在确定了男性总IgE的易感基因后，我们将通过对哥斯达黎加和CAMP的哮喘女孩家庭中新发现的候选基因进行关联研究，评估我们研究结果的普遍性。最后，我们将评估这些候选基因在CD4+ T淋巴细胞上的表达，并检查所选变异是否影响CAMP中哮喘儿童血清总IgE的基因表达特征。这一建议提供了一个独特的机会，以确定哮喘易感基因（S）的一般和西班牙裔美国人特别是。关于公共卫生相关性的声明尽管在美国和拉丁美洲的某些西班牙裔亚群中哮喘的负担不成比例，但对西班牙裔哮喘的遗传学知之甚少。该提案将利用最先进的遗传学和基因组学方法，以帮助了解总血清IgE的遗传调控的一个组成部分，总血清IgE是哮喘的关键中间体，一般来说，特别是在西班牙裔人中。 (End摘要）

DESCRIPTION (provided by applicant): Although asthma is a significant public health problem among Hispanics in the United States and in Latin America, little is known about the contribution of genetic factors to the pathogenesis of asthma in this ethnic group. We have previously identified significant evidence of linkage to total serum IgE on chromosome 20p12 among males in a genetically isolated Hispanic population in Costa Rica. This proposal seeks to identify genetic determinants of total serum IgE - a critical intermediate phenotype of asthma- on chromosome 20p12. We will first conduct a fine-mapping association analysis of total serum IgE on chromosome 20p12 in Costa Rican boys with asthma and their parents. We will then attempt to replicate positive findings among families of white (non-Hispanic) boys in the Childhood Asthma Management Program (CAMP). After identification of a susceptibility gene(s) for total IgE in males, we will assess the generalizability of our findings by performing association studies of newly identified candidate genes among families of girls with asthma in both Costa Rica and CAMP. Finally, we will assess the expression of these candidate genes on CD4+ T lymphocytes and examine whether selected variants affect gene expression signatures for total serum IgE among children with asthma in CAMP. This proposal offers a unique opportunity to identify an asthma-susceptibility gene(s) in general and among Hispanics in particular. STATEMENT ON PUBLIC HEALTH RELEVANCE Little is known about the genetics of asthma in Hispanics, despite the disproportionate burden of asthma in certain Hispanic subgroups in both the U.S. and in Latin America. This proposal will utilize state-of-the-art genetic and genomic approaches to help to understand a component of the genetic regulation of total serum IgE, a critical intermediate of asthma, in general and among Hispanics in particular. (End of Abstract)