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Autozygome and high throughput confirmation of disease genes candidacy
PURPOSE: Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752307/ https://www.ncbi.nlm.nih.gov/pubmed/30237576 http://dx.doi.org/10.1038/s41436-018-0138-x |
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author | Maddirevula, Sateesh Alzahrani, Fatema Al-Owain, Mohammed Al Muhaizea, Mohammad A. Kayyali, Husam R. AlHashem, Amal Rahbeeni, Zuhair Al-Otaibi, Maha Alzaidan, Hamad I. Balobaid, Ameera El Khashab, Heba Y. Bubshait, Dalal K. Faden, Maha Yamani, Suad Al Dabbagh, Omar Al-Mureikhi, Mariam Jasser, Abdulla Al Alsaif, Hessa S. Alluhaydan, Iram Seidahmed, Mohammed Zain Alabbasi, Bashair Hamza Almogarri, Ibrahim Kurdi, Wesam Akleh, Hana Qari, Alya Al Tala, Saeed M. Alhomaidi, Suzan Kentab, Amal Y. Salih, Mustafa A. Chedrawi, Aziza Alameer, Seham Tabarki, Brahim Shamseldin, Hanan E. Patel, Nisha Ibrahim, Niema Abdulwahab, Firdous Samira, Menasria Goljan, Ewa Abouelhoda, Mohamed Meyer, Brian F. Hashem, Mais Shaheen, Ranad AlShahwan, Saad Alfadhel, Majid Ben-Omran, Tawfeg Al-Qattan, Mohammad M. Monies, Dorota Alkuraya, Fowzan S. |
author_facet | Maddirevula, Sateesh Alzahrani, Fatema Al-Owain, Mohammed Al Muhaizea, Mohammad A. Kayyali, Husam R. AlHashem, Amal Rahbeeni, Zuhair Al-Otaibi, Maha Alzaidan, Hamad I. Balobaid, Ameera El Khashab, Heba Y. Bubshait, Dalal K. Faden, Maha Yamani, Suad Al Dabbagh, Omar Al-Mureikhi, Mariam Jasser, Abdulla Al Alsaif, Hessa S. Alluhaydan, Iram Seidahmed, Mohammed Zain Alabbasi, Bashair Hamza Almogarri, Ibrahim Kurdi, Wesam Akleh, Hana Qari, Alya Al Tala, Saeed M. Alhomaidi, Suzan Kentab, Amal Y. Salih, Mustafa A. Chedrawi, Aziza Alameer, Seham Tabarki, Brahim Shamseldin, Hanan E. Patel, Nisha Ibrahim, Niema Abdulwahab, Firdous Samira, Menasria Goljan, Ewa Abouelhoda, Mohamed Meyer, Brian F. Hashem, Mais Shaheen, Ranad AlShahwan, Saad Alfadhel, Majid Ben-Omran, Tawfeg Al-Qattan, Mohammad M. Monies, Dorota Alkuraya, Fowzan S. |
author_sort | Maddirevula, Sateesh |
collection | PubMed |
description | PURPOSE: Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. METHODS: Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders. CONCLUSIONS: Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing. |
format | Online Article Text |
id | pubmed-6752307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-67523072019-09-23 Autozygome and high throughput confirmation of disease genes candidacy Maddirevula, Sateesh Alzahrani, Fatema Al-Owain, Mohammed Al Muhaizea, Mohammad A. Kayyali, Husam R. AlHashem, Amal Rahbeeni, Zuhair Al-Otaibi, Maha Alzaidan, Hamad I. Balobaid, Ameera El Khashab, Heba Y. Bubshait, Dalal K. Faden, Maha Yamani, Suad Al Dabbagh, Omar Al-Mureikhi, Mariam Jasser, Abdulla Al Alsaif, Hessa S. Alluhaydan, Iram Seidahmed, Mohammed Zain Alabbasi, Bashair Hamza Almogarri, Ibrahim Kurdi, Wesam Akleh, Hana Qari, Alya Al Tala, Saeed M. Alhomaidi, Suzan Kentab, Amal Y. Salih, Mustafa A. Chedrawi, Aziza Alameer, Seham Tabarki, Brahim Shamseldin, Hanan E. Patel, Nisha Ibrahim, Niema Abdulwahab, Firdous Samira, Menasria Goljan, Ewa Abouelhoda, Mohamed Meyer, Brian F. Hashem, Mais Shaheen, Ranad AlShahwan, Saad Alfadhel, Majid Ben-Omran, Tawfeg Al-Qattan, Mohammad M. Monies, Dorota Alkuraya, Fowzan S. Genet Med Article PURPOSE: Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. METHODS: Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders. CONCLUSIONS: Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing. Nature Publishing Group US 2018-09-21 2019 /pmc/articles/PMC6752307/ /pubmed/30237576 http://dx.doi.org/10.1038/s41436-018-0138-x 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 Maddirevula, Sateesh Alzahrani, Fatema Al-Owain, Mohammed Al Muhaizea, Mohammad A. Kayyali, Husam R. AlHashem, Amal Rahbeeni, Zuhair Al-Otaibi, Maha Alzaidan, Hamad I. Balobaid, Ameera El Khashab, Heba Y. Bubshait, Dalal K. Faden, Maha Yamani, Suad Al Dabbagh, Omar Al-Mureikhi, Mariam Jasser, Abdulla Al Alsaif, Hessa S. Alluhaydan, Iram Seidahmed, Mohammed Zain Alabbasi, Bashair Hamza Almogarri, Ibrahim Kurdi, Wesam Akleh, Hana Qari, Alya Al Tala, Saeed M. Alhomaidi, Suzan Kentab, Amal Y. Salih, Mustafa A. Chedrawi, Aziza Alameer, Seham Tabarki, Brahim Shamseldin, Hanan E. Patel, Nisha Ibrahim, Niema Abdulwahab, Firdous Samira, Menasria Goljan, Ewa Abouelhoda, Mohamed Meyer, Brian F. Hashem, Mais Shaheen, Ranad AlShahwan, Saad Alfadhel, Majid Ben-Omran, Tawfeg Al-Qattan, Mohammad M. Monies, Dorota Alkuraya, Fowzan S. Autozygome and high throughput confirmation of disease genes candidacy |
title | Autozygome and high throughput confirmation of disease genes candidacy |
title_full | Autozygome and high throughput confirmation of disease genes candidacy |
title_fullStr | Autozygome and high throughput confirmation of disease genes candidacy |
title_full_unstemmed | Autozygome and high throughput confirmation of disease genes candidacy |
title_short | Autozygome and high throughput confirmation of disease genes candidacy |
title_sort | autozygome and high throughput confirmation of disease genes candidacy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752307/ https://www.ncbi.nlm.nih.gov/pubmed/30237576 http://dx.doi.org/10.1038/s41436-018-0138-x |
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