GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

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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.