Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population

Hideaki Moteki; Hela Azaiez; Kevin T Booth; A Eliot Shearer; Christina M Sloan; Diana L Kolbe; Shin-ya Nishio; Mitsuru Hattori; Shin-ichi Usami; Richard J H Smith

doi:10.1111/cge.12677

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Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population

Journal article

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Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population

Hideaki Moteki, Hela Azaiez, Kevin T Booth, A Eliot Shearer, Christina M Sloan, Diana L Kolbe, Shin-ya Nishio, Mitsuru Hattori, Shin-ichi Usami and Richard J H Smith

Clinical genetics, Vol.89(4), pp.466-472

04/2016

DOI: 10.1111/cge.12677

PMCID: PMC4783301

PMID: 26346818

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Abstract

Recent advances in targeted genomic enrichment with massively parallel sequencing (TGE+MPS) have made comprehensive genetic testing for non-syndromic hearing loss (NSHL) possible. After excluding NSHL subjects with causative mutations in GJB2 and the MT-RNR1 (1555A>G) variant by Sanger sequencing, we completed TGE+MPS on 194 probands with presumed NSHL identified across Japan. We used both publicly available minor allele frequency (MAF) datasets and ethnic-specific MAF filtering against an in-house database of 200 normal-hearing Japanese controls. Ethnic-specific MAF filtering allowed us to re-categorize as common 203 variants otherwise annotated as rare or novel in non-Japanese ethnicities. This step minimizes false-positive results and improves the annotation of identified variants. Causative variants were identified in 27% of probands with solve rates of 35%, 35% and 19% for dominant, recessive and sporadic NSHL, respectively. Mutations in MYO15A and CDH23 follow GJB2 as the frequent causes of recessive NSHL; copy number variations in STRC are a major cause of mild-to-moderate NSHL. Ethnic-specific filtering by allele frequency is essential to optimize the interpretation of genetic data.

ethnicity

deafness

massively parallel sequencing

targeted genomic enrichment

Hearing loss

Details

Title: Subtitle: Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population
Creators: Hideaki Moteki
Hela Azaiez
Kevin T Booth
A Eliot Shearer
Christina M Sloan
Diana L Kolbe
Shin-ya Nishio
Mitsuru Hattori
Shin-ichi Usami
Richard J H Smith
Resource Type: Journal article
Publication Details: Clinical genetics, Vol.89(4), pp.466-472
DOI: 10.1111/cge.12677
PMID: 26346818
PMCID: PMC4783301
NLM abbreviation: Clin Genet
ISSN: 0009-9163
eISSN: 1399-0004
Grant note: DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: DC003544, DC002842, DC012049
Language: English
Date published: 04/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984007166902771

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