GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

描述(改编自申请人的摘要)：该项目的长期目标 研究是寻找一个或多个与慢性中耳炎发生有关的基因 渗出性中耳炎(COME)和复发性中耳炎(ROM)，并识别 任何在这些疾病易感性中起作用的基因-环境相互作用 条件。与COME/ROM易感性相关的基因的发现将提供 洞察疾病的发病机理和致病机理，从而提示 新的治疗和预防策略。拥有遗传基因知识 易感性，高危儿童可能成为严格监测的目标 和积极的治疗，以防止来/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。 这项研究旨在证明家庭中COMe/ROM和ROM之间的联系 覆盖整个人类基因组的多态DNA标记。这项研究旨在 确定至少有两个兄弟姐妹且确诊为 COME/ROM的证据(通过病史、耳显微检查、 多频鼓室测压和医疗记录)，以及在有一个 受影响的兄弟姐妹和一个未受影响的兄弟姐妹。符合资格的家庭成员 中耳炎的家系研究将为DNA提取和 基因分型。届时将使用390个遗传标记进行基因组筛选 遗传病研究中心提供大约10厘米的地图 人类基因组。基因扫描和基因分型软件将用于读取凝胶 并对其进行了基因分型。对#年确定的联系领域进行重点评价 基因组范围的筛选将通过精细的遗传图谱来完成。随着时间推移 许可证，基因类型将在感兴趣的候选区域和基因座确定 可能与发病/发病有关。数据分析将包括受影响的 SIB对、不协调SIB对以及区间和多点映射。 受父母影响的后代三人组也将被分析是否存在关联 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.