This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this study is to find a gene or genes involved in the development of chronic/recurrent otitis media (COME/ROM) and to identify any gene-gene or gene-environment interactions that play a role in the 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 evidence of COME/ROM (ascertained by history, ear examination, multifrequency tympanometry, and medical record), and in families with one affected and one unaffected sibling. Families were recruited from several studies in which the proband was treated with tubes. A total of 591 DNA samples from 133 families (153 affected sib pairs, 138 discordant sib pairs and 95 affected relative pairs) underwent a 400 marker genome screen at the Center for Inherited Disease Research (CIDR). Analysis revealed significant linkage with COME/ROM at chromosome 3, 10, and 19. Focused evaluation of areas of linkage identified in the genome screen with dense genetic mapping, candidate gene analyses, and recruitment of 800 unrelated cases and controls for association analyses is and replication of family study results is ongoing.
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