GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

描述（改编自申请人的摘要）：本发明的长期目标是： 这项研究的目的是找到一个或多个与慢性中耳炎的发展有关的基因 中耳积液（COME）和复发性中耳炎（ROM），并确定 任何基因-环境相互作用在这些易感性中发挥作用， 条件发现与COME/ROM易感性相关的基因将提供 深入了解疾病的发病机理和病因机制，从而表明 新的治疗和预防策略。了解基因 易感性，高危儿童可作为严格监测的目标 积极治疗以预防COME/ROM后遗症，包括听力损失。 如果以儿童为目标，初级预防战略可能会更有效 有明确的遗传风险。 本研究旨在证明COME/ROM和 多态性DNA标记在整个人类基因组中。该研究旨在 确定至少有两个兄弟姐妹的家庭中的基因型， COME/ROM的证据（通过病史，耳显微镜检查， 多频鼓室压测定和医疗记录），并在家庭中有一个 受影响的和一个未受影响的兄弟姐妹。符合条件的家庭成员 中耳炎家族研究将提供血液样本用于DNA提取， 基因分型基因组筛查将在390个遗传标记中进行， 遗传疾病研究中心提供了一个大约10 cM的地图， 人类基因组将使用GeneScan和基因分型软件读取凝胶 并对基因型进行分类。重点评价 全基因组筛选将通过精细的遗传作图来完成。随着时间 如果允许，将在感兴趣的候选区域和位点确定基因型 可能与COME/ROM病因有关。数据分析将包括受影响的 同胞对、不一致同胞对以及间隔和多点映射。 父母影响的后代三人组也将进行连锁分析 不平衡

DESCRIPTION (Adapted from the Applicant's Abstract): The long-term goal of this study is to find a gene or genes involved in the development of chronic otitis media with effusion (COME) and recurrent otitis media (ROM), and to identify any gene-environment interactions that play a role in susceptibility to these conditions. Discovery of genes linked to COME/ROM susceptibility will provide insight into disease pathogenesis and etiologic mechanisms, thereby suggesting new treatment and prevention strategies. With knowledge of genetic susceptibility, high risk children could be targeted for rigorous surveillance and aggressive treatment to prevent COME/ROM sequelae including hearing loss. Primary prevention strategies could be more efficient if they targeted children with defined genetic risk. This study is designed to demonstrate linkage in families between COME/ROM and polymorphic DNA markers across the entire human genome. The study aims to determine genotypes in families with at least two siblings with confirmed evidence of COME/ROM (ascertained by history, otomicroscopic ear examination, multifrequency tympanometry, and medical record), and in families with one affected and one unaffected sibling. Members of eligible families from the Family Study of Otitis Media will provide blood samples for DNA extraction and genotyping. Genome screening will be performed with 390 genetic markers at the Center for Inherited Disease Research to provide an approximate 10 cM map of the human genome. GeneScan and Genotyping software will be used to read gels and classify genotypes. Focused evaluation of areas of linkage identified in the genome wide screen will be accomplished with fine genetic mapping. As time permits, genotypes will be determined at interesting candidate regions and loci potentially involved in COME/ROM etiology. Data analysis will include affected sib pair, discordant sib pair, and interval and multipoint mapping. Parent-affected offspring trios will also be analyzed for linkage disequilibrium.