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<a href="http://doi.org/10.1007/s10162-020-00762-3" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s10162-020-00762-3</a>
ISSN
1525-3961
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Update Year & Number
August 2020 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
NEOMED Postdoc Publications
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Title
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The genetics of variation of the wave 1 amplitude of the mouse auditory brainstem response
Publisher
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Jaro-Journal of the Association for Research in Otolaryngology
Subject
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injury; mice; eQTL; genome-wide association; strains; induced hearing-loss; architecture; traits; cochlear synaptopathy; gwas; hmdp; nihl; GWAS; HMDP; NIHL
Creator
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Boussaty EC; Gillard D; Lavinsky J; Salehi P; Wang J; Mendonca A; Allayee H; Manor ; Friedman RA
Description
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This is the first genome-wide association study with the Hybrid Mouse Diversity Panel (HDMP) to define the genetic landscape of the variation in the suprathreshold wave 1 amplitude of the auditory brainstem response (ABR) both pre- and post-noise exposure. This measure is correlated with the density of the auditory neurons (AN) and/or the compliment of synaptic ribbons within the inner hair cells of the mouse cochlea. We analyzed suprathreshold ABR for 635 mice from 102 HMDP strains pre- and post-noise exposure (108 dB 10 kHz octave band noise exposure for 2 h) using auditory brainstem response (ABR) wave 1 suprathreshold amplitudes as part of a large survey (Myint et al., Hear Res 332:113-120, 2016). Genome-wide significance levels for pre- and post-exposure wave 1 amplitude across the HMDP were performed using FaST-LMM. Synaptic ribbon counts (Ctbp2 and mGluR2) were analyzed for the extreme strains within the HMDP. ABR wave 1 amplitude varied across all strains of the HMDP with differences ranging between 2.42 and 3.82-fold pre-exposure and between 2.43 and 7.5-fold post-exposure with several tone burst stimuli (4 kHz, 8 kHz, 12 kHz, 16 kHz, 24 kHz, and 32 kHz). Immunolabeling of paired synaptic ribbons and glutamate receptors of strains with the highest and lowest wave 1 values pre- and post-exposure revealed significant differences in functional synaptic ribbon counts. Genome-wide association analysis identified genome-wide significant threshold associations on chromosome 3 (24 kHz; JAX00105429;p < 1.12E-06) and chromosome 16 (16 kHz; JAX00424604;p < 9.02E-07) prior to noise exposure and significant associations on chromosomes 2 (32 kHz; JAX00497967;p < 3.68E-08) and 13 (8 kHz; JAX00049416; 1.07E-06) after noise exposure. In order to prioritize candidate genes, we generatedcis-eQTLs from microarray profiling of RNA isolated from whole cochleae in 64 of the tested strains. This is the first report of a genome-wide association analysis, controlled for population structure, to explore the genetic landscape of suprathreshold wave 1 amplitude measurements of the mouse ABR. We have defined two genomic regions associated with wave 1 amplitude variation prior to noise exposure and an additional two associated with variation after noise exposure.
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<a href="http://doi.org/10.1007/s10162-020-00762-3" target="_blank" rel="noreferrer noopener">10.1007/s10162-020-00762-3</a>
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journalArticle
Allayee H
architecture
August 2020 List
Boussaty EC
cochlear synaptopathy
eQTL
Friedman RA
genome-wide association
Gillard D
gwas
hmdp
induced hearing-loss
Injury
Jaro-Journal of the Association for Research in Otolaryngology
journalArticle
Lavinsky J
Manor
Mendonca A
Mice
NEOMED College of Medicine Postdoc
NEOMED Postdoc Publications
nihl
Salehi P
strains
traits
Wang J