| Title |
Genome-Wide Association Analysis Identifies Dcc as an Essential Factor in the Innervation of the Peripheral Vestibular System in Inbred Mice
|
|---|---|
| Published in |
Journal of the Association for Research in Otolaryngology, August 2016
|
| DOI | 10.1007/s10162-016-0578-4 |
| Pubmed ID | |
| Authors |
Pezhman Salehi, Anthony Myint, Young J. Kim, Marshall X. Ge, Joel Lavinsky, Maria K. Ho, Amanda L. Crow, Charlene Cruz, Maya Monges-Hernadez, Juemei Wang, Jaana Hartiala, Li I. Zhang, Hooman Allayee, Aldons J. Lusis, Takahiro Ohyama, Rick A. Friedman |
| Abstract |
This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr. 18 (peak SNP rs29632020), one gene, deleted in colorectal carcinoma (Dcc) has a well-established role in nervous system development. An in-depth analysis of Dcc-deficient mice demonstrated elevation in mean VsEP threshold for Dcc (+/-) mice (-11.86 dB) compared to wild-type (-9.68 dB) littermates. Synaptic ribbon studies revealed Dcc (-/-) (P0) and Dcc (+/-) (6-week-old) mice showed lower density of the presynaptic marker (CtBP2) as compared to wild-type controls. Vestibular ganglion cell counts of Dcc (-/-) (P0) was lower than controls. Whole-mount preparations showed abnormal innervation of the utricle, saccule, and crista ampullaris at E14.5, E16.5, and E18.5. Postnatal studies were limited by the perinatal lethality in Dcc (-/-) mice. Expression analyses using in situ hybridization and immunohistochemistry showed Dcc expression in the mouse vestibular ganglion (E15.5), and utricle and crista ampullaris (6-week-old), respectively. In summary, we report the first GWAS for vestibular functional variation in inbred mice and provide evidence for the role of Dcc in the normal innervation of the peripheral vestibular system. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 5% |
| Unknown | 18 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 21% |
| Unspecified | 3 | 16% |
| Student > Ph. D. Student | 3 | 16% |
| Professor | 2 | 11% |
| Professor > Associate Professor | 2 | 11% |
| Other | 2 | 11% |
| Unknown | 3 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Unspecified | 3 | 16% |
| Agricultural and Biological Sciences | 3 | 16% |
| Neuroscience | 3 | 16% |
| Biochemistry, Genetics and Molecular Biology | 2 | 11% |
| Medicine and Dentistry | 2 | 11% |
| Other | 2 | 11% |
| Unknown | 4 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 August 2016.
All research outputs
#18,572,005
of 23,849,058 outputs
Outputs from Journal of the Association for Research in Otolaryngology
#309
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Outputs of similar age
#252,368
of 346,389 outputs
Outputs of similar age from Journal of the Association for Research in Otolaryngology
#5
of 8 outputs
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