GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

慢性/复发性中耳炎的遗传流行病学

• 批准号: 6784999
• 负责人: KATHLEEN Ann DALY
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6784999
• 关键词: blood chemistry; chronic disease /disorder; clinical research; disease /disorder etiology; exudate /transudate; gene environment interaction; genetic markers; genetic polymorphism; genetic susceptibility; genotype; human genetic material tag; human subject; linkage mapping; otitis media; relapse /recurrence; siblings

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.

描述（改编自申请人的摘要）：本项目的长期目标 研究的目的是寻找与慢性中耳炎的发展有关的一个或多个基因 渗出性中耳炎 (COME) 和复发性中耳炎 (ROM)，并识别 任何在这些因素的易感性中发挥作用的基因-环境相互作用 状况。发现与 COME/ROM 易感性相关的基因将提供 深入了解疾病发病机制和病因机制，从而提出 新的治疗和预防策略。有了遗传知识 易感性高危儿童可能成为严格监测的目标 积极治疗以预防 COME/ROM 后遗症，包括听力损失。 如果初级预防策略针对儿童可能会更有效 具有明确的遗传风险。 本研究旨在证明 COME/ROM 和家庭之间的联系 整个人类基因组的多态性 DNA 标记。该研究旨在 确定至少有两个兄弟姐妹患有确诊疾病的家庭的基因型 COME/ROM 的证据（通过病史、耳镜检查、 多频鼓室导抗测试和医疗记录），以及有一个家庭 受影响的和一名未受影响的兄弟姐妹。符合条件的家庭成员 中耳炎家庭研究将提供血液样本进行 DNA 提取和 基因分型。基因组筛查将在 390 个遗传标记上进行 遗传病研究中心提供大约 10 厘米的地图 人类基因组。 GeneScan 和基因分型软件将用于读取凝胶 并对基因型进行分类。对确定的联系领域进行重点评估 全基因组筛选将通过精细的遗传图谱来完成。随着时间 获得许可后，将在感兴趣的候选区域和基因座确定基因型 可能与 COME/ROM 病因学有关。数据分析将包括受影响的 同胞对、不一致同胞对以及区间和多点映射。 还将分析受父母影响的后代三人组的联系 不平衡。