COLLABORATIVE STUDIES ON THE GENETICS OF ASTHMA (CSGA)

哮喘是一种以气道可变为特征的呼吸系统疾病 阻塞、气道炎症和支气管高反应性 （渤海华美）。 哮喘死亡率和患病率有所增加 美国，尤其是非洲裔美国人。 多项研究表明 遗传和环境因素对哮喘都很重要 易感性。 遗传学合作研究的目的 哮喘（CSGA）是为了识别哮喘易感位点。 CSGA 是 由四个中心组成（约翰·霍普金斯大学、约翰霍普金斯大学 芝加哥大学、马里兰大学、明尼苏达大学和一个数据 Bowman Gray 协调中心）。 在每个中心，家庭都 通过两个患有哮喘的兄弟姐妹确定。 所有家庭成员 通过肺活量测定、支气管反应性来表征 乙酰甲胆碱或可逆性测试、皮试和问卷数据。 首批 237 名同胞的初始基因组筛选已完成 来自三个种族群体（非裔美国人、白种人和 西班牙裔），并对其余家庭成员进行基因分型 家庭将在更新提案开始之前完成。 因此，CSGA 的最初目标是绘制易感区域图 已完成，检测到多种新型染色体 区域，以及先前链接到的几个区域的复制 相关的表型。 为了确定这些的重要性 哮喘易感性地区以及环境风险的影响 因素，我们建议 1）评估关联的证据 使用 2 点、多点和多位点完成 CSGA 数据 治疗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试反应性）； 2）使用额外的遗传对区域进行精细绘图研究 标记以获得 <2 cmM 图谱； 3）确定候选基因和新基因 序列变体； 4) 描述患者群体的特征 哮喘研究已确定的与哮喘严重程度有关的变异 支气管炎症。 这些研究将使美国能够识别哮喘 易感基因及其变异体，与其他基因的相互作用 和环境风险因素，并为 开发改进的治疗方法并最终预防 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.