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Publication : The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants.

First Author  Crow AL Year  2015
Journal  G3 (Bethesda) Volume  5
Issue  11 Pages  2329-39
PubMed ID  26342000 Mgi Jnum  J:244922
Mgi Id  MGI:5913701 Doi  10.1534/g3.115.021592
Citation  Crow AL, et al. (2015) The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants. G3 (Bethesda) 5(11):2329-39
abstractText  Genome-wide association studies (GWAS) have been successfully applied in humans for the study of many complex phenotypes. However, identification of the genetic determinants of hearing in adults has been hampered, in part, by the relative inability to control for environmental factors that might affect hearing throughout the lifetime, as well as a large degree of phenotypic heterogeneity. These and other factors have limited the number of large-scale studies performed in humans that have identified candidate genes that contribute to the etiology of this complex trait. To address these limitations, we performed a GWAS analysis using a set of inbred mouse strains from the Hybrid Mouse Diversity Panel. Among 99 strains characterized, we observed approximately two-fold to five-fold variation in hearing at six different frequencies, which are differentiated biologically from each other by the location in the cochlea where each frequency is registered. Among all frequencies tested, we identified a total of nine significant loci, several of which contained promising candidate genes for follow-up study. Taken together, our results indicate the existence of both genes that affect global cochlear function, as well as anatomical- and frequency-specific genes, and further demonstrate the complex nature of mammalian hearing variation.
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