GENETICS OF ASTHMA

哮喘是一种常见的临床疾病，其特征是可逆性。 呼吸道阻塞，这是一种日益严重的 导致美国普通人群发病和死亡的原因。这个 人口中哮喘的患病率估计在3%- 5%，儿童年龄在3-11岁之间的风险最大。 两性和所有种族群体都受到同样的影响。 此应用程序的总体目标是响应 L将开启跨学科分子遗传学 对12个大的、被广泛研究的哮喘家系的研究。我们 建议进一步描述临床特征和参数 在我们之前确认的哮喘家系中与哮喘相关，收集 处理家庭成员的血液样本，检查和重新测试每一个 使用NHLBI批准的哮喘诊断方案和 相关发现，收集环境和职业史 数据，建立永生细胞系，基因信息谱系 成员使用重复序列(GT)n DNA多态，并执行 数据的统计遗传分析。 我们已经确定了12个适合进行基因定位的家系，每个家系 已经被我们跟踪了超过25年。这些血统中的许多人都有 在选定的遗传标记、皮肤方面具有高度的特征 对常见的空气过敏原、IgE水平(总的和特异性的)进行检测， 体检和肺功能。这些人中的大多数 20多年来，每年都会对谱系进行追踪。我们 已经成功地联系了每个 12个确定的家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 是根据人口、双胞胎和家庭研究的证据提出的。 根据积累的数据，多种细胞类型和众多 细胞调控机制影响哮喘的发生发展及其机制 对治疗的反应。既有复杂表型(哮喘)，也有中间型 表型(特应性、特异性免疫反应、血清IgE水平、介质 释放，支气管高反应性)将用于研究遗传 观察到的哮喘临床证候易感性。我们的中央 假设哮喘在表型和表型上都是异质性的。 基因水平；然而，在我们信息丰富的谱系中， 利用(GT)n重复多态和健壮同胞对的连锁策略 分析方法，将使我们能够识别潜在的基因座 对哮喘及其成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.