Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with frequency-specific effects on the hearing spectrum of NIH Swiss mice

BMC Genetics

Research Article

Konrad Noben-Trauth¹  James M Keller¹ 

[1] Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, 20850, Rockville, MD, USA;

关键词: NIH Swiss;    Sensorineural hearing loss;    Quantitative trait loci analyses;    Tonotopy;    DPOAE;   

DOI  :  10.1186/1471-2156-13-32

 received in 2012-01-10, accepted in 2012-03-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations.ResultsWe identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum.ConclusionsThis study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea.

【 授权许可】

Unknown   
© The article is a work of the United States Government; Title U.S.C 5 105 provides that copyright protection is not available for any work of the United States government in the United States; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.