GENETICS OF ASTHMA

哮喘是一种常见的临床疾病，其特征在于可逆性哮喘。 支气管气道阻塞，这是一个日益严重的 美国普通人群发病率和死亡率的原因。 的 哮喘在人群中的患病率估计为3% - 5%，3 - 11岁的儿童风险最大。 男女和所有种族群体同样受到影响。 本申请的总体目标是 RFA-NIH-92-HL-04-L是启动跨学科的分子遗传学 在12个大的，广泛研究的家系中进行的哮喘研究。 我们 建议进一步表征临床特征和参数 在我们先前确定的家系中与哮喘相关，收集 处理家庭成员的血液样本， 使用NHLBI批准的哮喘诊断方案的成员， 相关发现，收集环境和职业史 数据，建立永生化细胞系，基因型信息谱系 成员使用重复序列（GT）n DNA多态性，并执行 数据的遗传统计分析。 我们已经确定了12个适合基因定位的家系， 已经被我们关注了25年 这些血统中的许多都有 在选定的遗传标记、皮肤、 测试常见的空气过敏原，IgE水平（总和特定）， 体格检查和肺功能 大多数人在这些 在过去的20年里，每年都对谱系进行跟踪。 我们 我已经成功地联系了每一个人， 12个确定的谱系，并已获得他们的同意， 参与这项研究。 哮喘易感性的遗传成分的存在， 从人口、双胞胎和家庭研究的证据中可以看出。 根据积累的数据，多种细胞类型和许多 细胞控制机制影响哮喘的发展及其 对治疗的反应 复杂表型（哮喘）和中间型 表型（特应性、特异性免疫应答、血清IgE水平、介导因子 释放，支气管高反应性）将用于研究遗传 观察哮喘临床综合征的易感性。 我们的中央 假设哮喘在表型和 基因水平;然而，在我们的信息谱系中， 连锁策略，使用（GT）n重复多态性和强大的同胞对 分析方法，将使我们能够确定潜在的基因座， 对哮喘及其组分表型的单一或多重影响。

Asthma is a common clinical disorder characterized by reversible obstruction of the bronchial airways which is an increasingly serious cause of morbidity and mortality in the general U.S. population. The prevalence of asthma in the population is estimated to range from 3% - 5%, with children between the ages of 3 - 11 years are at greatest risk. Both sexes and all racial groups equally affected . The overall objective of this application in response to RFA-NIH-92-HL-04-L is to initiate interdisciplinary molecular genetic studies of asthma in twelve large, extensively studied pedigrees. We propose to further characterize the clinical features and parameters associated with asthma in our previously identified pedigrees, collect and process blood samples from family members, review and retest each member using NHLBI approved protocols for diagnosis of asthma and associated findings , collect environmental and occupational history data, establish immortalized cell lines, genotype informative pedigree members using repetitive sequence (GT)n DNA polymorphisms, and perform statistical genetic analyses of the data. We have identified 12 pedigrees suitable for gene mapping, each of which has been followed by us for over 25 years. Many of these pedigrees have been highly characterized with respect to selected genetic markers, skin testing to common aeroallergens, IgE levels (total and specific), physical examination, and pulmonary function. Most individuals in these pedigrees have been followed on a yearly basis for over 20 years. We have already successfully contacted multiple individuals in each of the twelve ascertained pedigrees and have obtained their consent to participate in this study. The presence of a genetic component to the susceptibility of asthma has been suggested from evidence of population, twin, and family studies. Based upon the accumulated data, multiple cell types and numerous cellular control mechanisms influence the development of asthma and its response to treatment. Both complex phenotypes (asthma) and intermediate phenotypes (atopy, specific immune responses, serum IgE levels, mediator release, bronchial hyperreactivity) will used to investigate genetic susceptibility of the observed clinical syndrome of asthma. Our central hypothesis is that asthma is heterogeneous at both the phenotypic and genetic level; yet, in our informative pedigrees, the application of the linkage strategy, using (GT)n repeat polymorphisms and robust sib pair method of analysis, will allow us to identify potential loci that have single or multiple effects on asthma and its component phenotypes.