Autozygome and high throughput confirmation of disease genes candidacy.
Sateesh Maddirevula, Fatema Alzahrani, Mohammed Al-Owain, Mohammad A Al Muhaizea, Husam R Kayyali, Amal AlHashem, Zuhair Rahbeeni, Maha Al-Otaibi, Hamad I Alzaidan, Ameera Balobaid, Heba Y El Khashab, Dalal K Bubshait, Maha Faden, Suad Al Yamani, Omar Dabbagh, Mariam Al-Mureikhi, Abdulla Al Jasser, Hessa S Alsaif, Iram Alluhaydan, Mohammed Zain Seidahmed, Bashair Hamza Alabbasi, Ibrahim Almogarri, Wesam Kurdi, Hana Akleh, Alya Qari, Saeed M Al Tala, Suzan Alhomaidi, Amal Y Kentab, Mustafa A Salih, Aziza Chedrawi, Seham Alameer, Brahim Tabarki, Hanan E Shamseldin, Nisha Patel, Niema Ibrahim, Firdous Abdulwahab, Menasria Samira, Ewa Goljan, Mohamed Abouelhoda, Brian F Meyer, Mais Hashem, Ranad Shaheen, Saad AlShahwan, Majid Alfadhel, Tawfeg Ben-Omran, Mohammad M Al-Qattan, Dorota Monies, Fowzan S Alkuraya
Genetics in medicine : official journal of the American College of Medical Genetics 2019 MarEstablishing 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. 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. 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. Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing.
Citation
Sateesh Maddirevula, Fatema Alzahrani, Mohammed Al-Owain, Mohammad A Al Muhaizea, Husam R Kayyali, Amal AlHashem, Zuhair Rahbeeni, Maha Al-Otaibi, Hamad I Alzaidan, Ameera Balobaid, Heba Y El Khashab, Dalal K Bubshait, Maha Faden, Suad Al Yamani, Omar Dabbagh, Mariam Al-Mureikhi, Abdulla Al Jasser, Hessa S Alsaif, Iram Alluhaydan, Mohammed Zain Seidahmed, Bashair Hamza Alabbasi, Ibrahim Almogarri, Wesam Kurdi, Hana Akleh, Alya Qari, Saeed M Al Tala, Suzan Alhomaidi, Amal Y Kentab, Mustafa A Salih, Aziza Chedrawi, Seham Alameer, Brahim Tabarki, Hanan E Shamseldin, Nisha Patel, Niema Ibrahim, Firdous Abdulwahab, Menasria Samira, Ewa Goljan, Mohamed Abouelhoda, Brian F Meyer, Mais Hashem, Ranad Shaheen, Saad AlShahwan, Majid Alfadhel, Tawfeg Ben-Omran, Mohammad M Al-Qattan, Dorota Monies, Fowzan S Alkuraya. Autozygome and high throughput confirmation of disease genes candidacy. Genetics in medicine : official journal of the American College of Medical Genetics. 2019 Mar;21(3):736-742
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PMID: 30237576
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