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

Clinical Genetics
Hideaki MotekiR J H Smith

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.

References

Mar 9, 2005·Lancet·Richard J H SmithKarl R White
Jun 21, 2005·Lancet·Margaret Rennels, Larry K Pickering
May 19, 2006·The New England Journal of Medicine·Cynthia C Morton, Walter E Nance
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
May 26, 2010·Clinical Genetics·K TsukadaUNKNOWN Deafness Gene Study Consortium
Nov 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·A Eliot ShearerRichard J H Smith
Feb 1, 2012·Human Mutation·Peter FrommoltPeter Nürnberg
May 9, 2012·BMC Biotechnology·Aiden Eliot ShearerRichard J H Smith
Jun 28, 2012·American Journal of Medical Genetics. Part a·Zohreh FattahiHossein Najmabadi
Jul 7, 2012·Science·Ferran Casals, Jaume Bertranpetit
Jun 28, 2013·Journal of Medical Genetics·A Eliot ShearerRichard J H Smith
Jun 26, 2014·Genome Medicine·A Eliot ShearerRichard J H Smith
Sep 30, 2014·American Journal of Human Genetics·A Eliot ShearerRichard J H Smith
Mar 20, 2015·The Annals of Otology, Rhinology, and Laryngology·Shin-Ya Nishio, Shin-Ichi Usami

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Citations

Dec 12, 2018·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Guillaume JouretAnne-Sophie Lebre
Apr 7, 2017·Scientific Reports·Jinsei JungJae Young Choi
Sep 28, 2017·Orphanet Journal of Rare Diseases·Nobuko YamamotoTatsuo Matsunaga
Dec 20, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Khushnooda RamzanFaiqa Imtiaz
Jul 5, 2016·Human Mutation·Atteeq U RehmanThomas B Friedman
Nov 5, 2021·Frontiers in Genetics·Shasha HuangYongyi Yuan
Nov 27, 2021·Journal of Human Genetics·Natsumi UeharaShin-Ichi Usami

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