COLLABORATIVE STUDIES ON THE GENETICS OF ASTHMA (CSGA)

哮喘是一种呼吸道疾病，其特征是气道可变 阻塞、气道炎症和支气管高反应性 （BHR）。 哮喘的死亡率和患病率都有所增加， 美国，尤其是非洲裔美国人。 多项研究表明， 遗传和环境因素在哮喘中都很重要 易感性 遗传学合作研究的目的是 哮喘（CSGA）是确定哮喘易感基因位点。 CSGA是 由四个中心组成（约翰霍普金斯大学， 芝加哥、马里兰州大学、明尼苏达大学和一个数据 Bowman Gray的协调中心）。 在每个中心， 通过两个患有哮喘的兄弟姐妹确定的。 所有家庭成员 肺功能测定、支气管对 乙酰甲胆碱或可逆性试验、皮肤试验和问卷调查数据。 第一个237个同胞的初步基因组筛选已经完成 来自三个种族群体（非洲裔美国人，高加索人， 西班牙裔），其余家庭成员的基因分型， 家庭将在更新建议开始之前完成。 因此，CSGA绘制易感区域的最初目标是 已经完成，检测到几种新的染色体 区域，并复制以前与 相关表型 为了确定其重要性， 哮喘易感地区，以及环境风险的影响 因素，我们建议1）评估证据的联系， 使用2点、多点和多位点完成CSGA数据 用于哮喘和相关表型的方法（包括BHR， 总血清IgE和对标准化过敏原的皮肤试验反应性）; 2)使用额外的遗传学方法对区域进行精细绘图研究 标记以获得<2cM的图谱; 3）鉴定候选基因和新的 序列变体;和4）表征患者群体， 研究哮喘严重程度方面已确定的变异， 支气管炎症 这些研究将使我们能够识别哮喘 易感基因及其变体，与其他基因的相互作用 和环境风险因素，并提供洞察力 发展更好的治疗和最终预防 哮喘

Asthma is a respiratory disease characterized by variable airways obstruction, airways inflammation and bronchial hyperresponsiveness (BHR). There are increases in asthma mortality and prevalence in the US, especially in African-Americans. Multiple studies suggest that both genetic and environmental factors are important in asthma susceptibility. The aim of the Collaborative Study of the Genetics of Asthma (CSGA) is to identify asthma susceptibility loci. The CSGA is composed of four centers (Johns Hopkins University, university of Chicago, University of Maryland, University of Minnesota, and a data coordinating center at Bowman Gray). At each center, families were ascertained through two siblings with asthma. All family members were characterized with spirometry, bronchial responsiveness to methacholine or reversibility testing, skin-tests and questionnaire data. The initial genome screen has been completed on the first 237 sib pairs from three racial groups (African-American, Caucasian, and Hispanic), and genotyping on the remaining family members and families will be completed before the start of the renewal proposal. Therefore, the initial aim of the CSGA to map susceptibility regions has been completed, with detection of several novel chromosomal regions, and replication of several regions previously linked to associated phenotypes. In order to determine the importance of these regions in asthma susceptibility, and the impact of environmental risk factors, we propose to 1) evaluate the evidence for linkage in the complete CSGA data using 2-point, multipoint and multilocus approaches for asthma and associated phenotypes (including BHR, total serum IgE and skin test reactivity to standardized allergens); 2)perform fine mapping studies of regions using additional genetic markers to obtain a <2 cM map; 3) identify candidate genes and novel sequence variants; and 4) characterize a patient population with asthma to study identified variants with respect to asthma severity and bronchial inflammation. These studies will allow US to identify asthma susceptibility genes and their variants, interactions with other genes and environmental risk factors, as well as provide insight for the development of improved treatment and ultimate prevention of asthma.