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Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families

BACKGROUND: Identification of genes responsible for medically important traits is a major challenge in human genetics. Due to the genetic heterogeneity of hearing loss, targeted DNA capture and massively parallel sequencing are ideal tools to address this challenge. Our subjects for genome analysis...

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Autores principales: Brownstein, Zippora, Friedman, Lilach M, Shahin, Hashem, Oron-Karni, Varda, Kol, Nitzan, Rayyan, Amal Abu, Parzefall, Thomas, Lev, Dorit, Shalev, Stavit, Frydman, Moshe, Davidov, Bella, Shohat, Mordechai, Rahile, Michele, Lieberman, Sari, Levy-Lahad, Ephrat, Lee, Ming K, Shomron, Noam, King, Mary-Claire, Walsh, Tom, Kanaan, Moien, Avraham, Karen B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308052/
https://www.ncbi.nlm.nih.gov/pubmed/21917145
http://dx.doi.org/10.1186/gb-2011-12-9-r89
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author Brownstein, Zippora
Friedman, Lilach M
Shahin, Hashem
Oron-Karni, Varda
Kol, Nitzan
Rayyan, Amal Abu
Parzefall, Thomas
Lev, Dorit
Shalev, Stavit
Frydman, Moshe
Davidov, Bella
Shohat, Mordechai
Rahile, Michele
Lieberman, Sari
Levy-Lahad, Ephrat
Lee, Ming K
Shomron, Noam
King, Mary-Claire
Walsh, Tom
Kanaan, Moien
Avraham, Karen B
author_facet Brownstein, Zippora
Friedman, Lilach M
Shahin, Hashem
Oron-Karni, Varda
Kol, Nitzan
Rayyan, Amal Abu
Parzefall, Thomas
Lev, Dorit
Shalev, Stavit
Frydman, Moshe
Davidov, Bella
Shohat, Mordechai
Rahile, Michele
Lieberman, Sari
Levy-Lahad, Ephrat
Lee, Ming K
Shomron, Noam
King, Mary-Claire
Walsh, Tom
Kanaan, Moien
Avraham, Karen B
author_sort Brownstein, Zippora
collection PubMed
description BACKGROUND: Identification of genes responsible for medically important traits is a major challenge in human genetics. Due to the genetic heterogeneity of hearing loss, targeted DNA capture and massively parallel sequencing are ideal tools to address this challenge. Our subjects for genome analysis are Israeli Jewish and Palestinian Arab families with hearing loss that varies in mode of inheritance and severity. RESULTS: A custom 1.46 MB design of cRNA oligonucleotides was constructed containing 246 genes responsible for either human or mouse deafness. Paired-end libraries were prepared from 11 probands and bar-coded multiplexed samples were sequenced to high depth of coverage. Rare single base pair and indel variants were identified by filtering sequence reads against polymorphisms in dbSNP132 and the 1000 Genomes Project. We identified deleterious mutations in CDH23, MYO15A, TECTA, TMC1, and WFS1. Critical mutations of the probands co-segregated with hearing loss. Screening of additional families in a relevant population was performed. TMC1 p.S647P proved to be a founder allele, contributing to 34% of genetic hearing loss in the Moroccan Jewish population. CONCLUSIONS: Critical mutations were identified in 6 of the 11 original probands and their families, leading to the identification of causative alleles in 20 additional probands and their families. The integration of genomic analysis into early clinical diagnosis of hearing loss will enable prediction of related phenotypes and enhance rehabilitation. Characterization of the proteins encoded by these genes will enable an understanding of the biological mechanisms involved in hearing loss.
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spelling pubmed-33080522012-03-20 Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families Brownstein, Zippora Friedman, Lilach M Shahin, Hashem Oron-Karni, Varda Kol, Nitzan Rayyan, Amal Abu Parzefall, Thomas Lev, Dorit Shalev, Stavit Frydman, Moshe Davidov, Bella Shohat, Mordechai Rahile, Michele Lieberman, Sari Levy-Lahad, Ephrat Lee, Ming K Shomron, Noam King, Mary-Claire Walsh, Tom Kanaan, Moien Avraham, Karen B Genome Biol Research BACKGROUND: Identification of genes responsible for medically important traits is a major challenge in human genetics. Due to the genetic heterogeneity of hearing loss, targeted DNA capture and massively parallel sequencing are ideal tools to address this challenge. Our subjects for genome analysis are Israeli Jewish and Palestinian Arab families with hearing loss that varies in mode of inheritance and severity. RESULTS: A custom 1.46 MB design of cRNA oligonucleotides was constructed containing 246 genes responsible for either human or mouse deafness. Paired-end libraries were prepared from 11 probands and bar-coded multiplexed samples were sequenced to high depth of coverage. Rare single base pair and indel variants were identified by filtering sequence reads against polymorphisms in dbSNP132 and the 1000 Genomes Project. We identified deleterious mutations in CDH23, MYO15A, TECTA, TMC1, and WFS1. Critical mutations of the probands co-segregated with hearing loss. Screening of additional families in a relevant population was performed. TMC1 p.S647P proved to be a founder allele, contributing to 34% of genetic hearing loss in the Moroccan Jewish population. CONCLUSIONS: Critical mutations were identified in 6 of the 11 original probands and their families, leading to the identification of causative alleles in 20 additional probands and their families. The integration of genomic analysis into early clinical diagnosis of hearing loss will enable prediction of related phenotypes and enhance rehabilitation. Characterization of the proteins encoded by these genes will enable an understanding of the biological mechanisms involved in hearing loss. BioMed Central 2011 2011-09-14 /pmc/articles/PMC3308052/ /pubmed/21917145 http://dx.doi.org/10.1186/gb-2011-12-9-r89 Text en Copyright ©2011 Brownstein et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Brownstein, Zippora
Friedman, Lilach M
Shahin, Hashem
Oron-Karni, Varda
Kol, Nitzan
Rayyan, Amal Abu
Parzefall, Thomas
Lev, Dorit
Shalev, Stavit
Frydman, Moshe
Davidov, Bella
Shohat, Mordechai
Rahile, Michele
Lieberman, Sari
Levy-Lahad, Ephrat
Lee, Ming K
Shomron, Noam
King, Mary-Claire
Walsh, Tom
Kanaan, Moien
Avraham, Karen B
Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title_full Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title_fullStr Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title_full_unstemmed Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title_short Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
title_sort targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308052/
https://www.ncbi.nlm.nih.gov/pubmed/21917145
http://dx.doi.org/10.1186/gb-2011-12-9-r89
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