COLLABORATIVE STUDIES ON THE GENETICS OF ASTHMA (CSGA)

哮喘是一种呼吸道疾病，其特征是呼吸道可变。 阻塞、呼吸道炎症和支气管高反应性 (Bhr)。在中国，哮喘死亡率和患病率有所增加 美国，尤其是非裔美国人。多项研究表明， 遗传和环境因素在哮喘发病中都很重要 敏感度。人类遗传学合作研究的目的 哮喘(CSGA)是对哮喘易感部位进行识别。CSGA是 由四个中心组成(约翰霍普金斯大学、霍普金斯大学 芝加哥大学、马里兰大学、明尼苏达大学和一项数据 鲍曼·格雷协调中心)。在每个中心，家庭都是 通过两个患有哮喘的兄弟姐妹确诊。所有家庭成员 以肺活量、支气管反应性为特征 乙酰甲胆碱或可逆性试验、皮肤试验和问卷调查数据。 最初的基因组筛查已经在第一个237个同胞身上完成 来自三个种族群体(非裔美国人、高加索人和 西班牙裔)，对其余家庭成员进行基因分型 家庭将在更新提案开始前完成。 因此，CSGA的最初目标是绘制易感区域 已经完成，检测到了几个新的染色体 区域，以及先前链接到的多个区域的复制 相关表型。为了确定这些因素的重要性 哮喘易感地区以及环境风险的影响 因素，我们建议1)评估在 使用两点、多点和多轨迹完成CSGA数据 哮喘及其相关表型的治疗方法(包括BHR， 血清总IgE和皮试对标准变应原的反应性)； 2)使用额外的基因对区域进行精细的测绘研究 获得2 cM图谱的标记；3)识别候选基因和新基因 序列变异；以及4)描述患者群体的特征 研究与哮喘严重程度和哮喘严重程度相关的已识别变种 支气管炎。这些研究将使美国能够识别哮喘 易感基因及其变异、与其他基因的相互作用 和环境风险因素，以及为 发展改进的治疗方法和最终预防 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.