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Genetics of hearing loss in the Arab population of Northern Israel
For multiple generations, much of the Arab population of Northern Israel has lived in communities with consanguineous marriages and large families. These communities have been particularly cooperative and informative for understanding the genetics of recessive traits. We studied the genetics of hear...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244407/ https://www.ncbi.nlm.nih.gov/pubmed/30139988 http://dx.doi.org/10.1038/s41431-018-0218-z |
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author | Danial-Farran, Nada Brownstein, Zippora Gulsuner, Suleyman Tammer, Luna Khayat, Morad Aleme, Ola Chervinsky, Elena Zoubi, Olfat Aboleile Walsh, Tom Ast, Gil King, Mary-Claire Avraham, Karen B. Shalev, Stavit A. |
author_facet | Danial-Farran, Nada Brownstein, Zippora Gulsuner, Suleyman Tammer, Luna Khayat, Morad Aleme, Ola Chervinsky, Elena Zoubi, Olfat Aboleile Walsh, Tom Ast, Gil King, Mary-Claire Avraham, Karen B. Shalev, Stavit A. |
author_sort | Danial-Farran, Nada |
collection | PubMed |
description | For multiple generations, much of the Arab population of Northern Israel has lived in communities with consanguineous marriages and large families. These communities have been particularly cooperative and informative for understanding the genetics of recessive traits. We studied the genetics of hearing loss in this population, evaluating 168 families from 46 different villages. All families were screened for founder variants by Sanger sequencing and 13 families were further evaluated by sequencing all known genes for hearing loss using our targeted gene panel HEar-Seq. Deafness in 34 of 168 families (20%) was explained by founder variants in GJB2, SLC26A4, or OTOF. In 6 of 13 families (46%) evaluated using HEar-Seq, deafness was explained by damaging alleles of SLC26A4, MYO15A, OTOG, LOXHD1, and TBC1D24. In some genes critical to hearing, it is particularly difficult to interpret variants that might affect splicing, because the genes are not expressed in accessible tissue. To address this problem for possible splice-altering variants of MYO15A, we evaluated minigenes transfected into HEK293 cells. Results revealed exon skipping in the message of MYO15A c.9083+6T>A, and intron retention in the message of MYO15A c.8340G>A, in each case leading to a premature stop and consistent with co-segregation of homozygosity for each variant with hearing loss. The profile of genetics of hearing loss in this population reflects the genetic heterogeneity of hearing loss and the usefulness of synthetic technologies to evaluate potentially causal variants in genes not expressed in accessible tissues. |
format | Online Article Text |
id | pubmed-6244407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-62444072018-11-21 Genetics of hearing loss in the Arab population of Northern Israel Danial-Farran, Nada Brownstein, Zippora Gulsuner, Suleyman Tammer, Luna Khayat, Morad Aleme, Ola Chervinsky, Elena Zoubi, Olfat Aboleile Walsh, Tom Ast, Gil King, Mary-Claire Avraham, Karen B. Shalev, Stavit A. Eur J Hum Genet Article For multiple generations, much of the Arab population of Northern Israel has lived in communities with consanguineous marriages and large families. These communities have been particularly cooperative and informative for understanding the genetics of recessive traits. We studied the genetics of hearing loss in this population, evaluating 168 families from 46 different villages. All families were screened for founder variants by Sanger sequencing and 13 families were further evaluated by sequencing all known genes for hearing loss using our targeted gene panel HEar-Seq. Deafness in 34 of 168 families (20%) was explained by founder variants in GJB2, SLC26A4, or OTOF. In 6 of 13 families (46%) evaluated using HEar-Seq, deafness was explained by damaging alleles of SLC26A4, MYO15A, OTOG, LOXHD1, and TBC1D24. In some genes critical to hearing, it is particularly difficult to interpret variants that might affect splicing, because the genes are not expressed in accessible tissue. To address this problem for possible splice-altering variants of MYO15A, we evaluated minigenes transfected into HEK293 cells. Results revealed exon skipping in the message of MYO15A c.9083+6T>A, and intron retention in the message of MYO15A c.8340G>A, in each case leading to a premature stop and consistent with co-segregation of homozygosity for each variant with hearing loss. The profile of genetics of hearing loss in this population reflects the genetic heterogeneity of hearing loss and the usefulness of synthetic technologies to evaluate potentially causal variants in genes not expressed in accessible tissues. Springer International Publishing 2018-08-23 2018-12 /pmc/articles/PMC6244407/ /pubmed/30139988 http://dx.doi.org/10.1038/s41431-018-0218-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Danial-Farran, Nada Brownstein, Zippora Gulsuner, Suleyman Tammer, Luna Khayat, Morad Aleme, Ola Chervinsky, Elena Zoubi, Olfat Aboleile Walsh, Tom Ast, Gil King, Mary-Claire Avraham, Karen B. Shalev, Stavit A. Genetics of hearing loss in the Arab population of Northern Israel |
title | Genetics of hearing loss in the Arab population of Northern Israel |
title_full | Genetics of hearing loss in the Arab population of Northern Israel |
title_fullStr | Genetics of hearing loss in the Arab population of Northern Israel |
title_full_unstemmed | Genetics of hearing loss in the Arab population of Northern Israel |
title_short | Genetics of hearing loss in the Arab population of Northern Israel |
title_sort | genetics of hearing loss in the arab population of northern israel |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244407/ https://www.ncbi.nlm.nih.gov/pubmed/30139988 http://dx.doi.org/10.1038/s41431-018-0218-z |
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