Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank

<h3>Purpose</h3><p dir="ltr">To date, approximately 1400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2% to 3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessi...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Geethanjali Devadoss Gandhi (14780425) (author)
مؤلفون آخرون: Elbay Aliyev (14056972) (author), Najeeb Syed (12561967) (author), Fazulur Rehaman Vempalli (14778577) (author), Chadi Saad (5369351) (author), Hamdi Mbarek (134997) (author), Omayma Al-Saei (18288931) (author), Aljazi Al-Maraghi (14056975) (author), Mona Abdi (10196665) (author), Navaneethakrishnan Krishnamoorthy (391608) (author), Ramin Badii (491543) (author), Said I. Ismail (11721428) (author), Wadha Al-Muftah (14152551) (author), Radja Badji (14152548) (author), Dima Darwish (14152545) (author), Tasnim Fadl (14152533) (author), Heba Yasin (14152542) (author), Maryem Ennaifar (14778556) (author), Rania Abdellatif (18589450) (author), Fatima Alkuwari (14778562) (author), Muhammad Alvi (4831311) (author), Yasser Al-Sarraj (11721425) (author), Asmaa Althani (499903) (author), Eleni Fethnou (14778568) (author), Fatima Qafoud (14778571) (author), Eiman Alkhayat (14778574) (author), Nahla Afifi (193245) (author), Sara Tomei (3441323) (author), Wei Liu (20030) (author), Stephan Lorenz (466378) (author), Hakeem Almabrazi (6561371) (author), Ramzi Temanni (671528) (author), Tariq Abu Saqri (14778580) (author), Mohammedhusen Khatib (14778583) (author), Mehshad Hamza (14778586) (author), Tariq Abu Zaid (14778589) (author), Ahmed El Khouly (14778592) (author), Tushar Pathare (14778595) (author), Shafeeq Poolat (14778598) (author), Rashid Al-Ali (846229) (author), Omar Albagha (8977856) (author), Souhaila Al-Khodor (247417) (author), Mashael Alshafai (14778607) (author), Lotfi Chouchane (61840) (author), Xavier Estivill (23803) (author), Khalid A. Fakhro (3158862) (author), Younes Mokrab (6367) (author), Jithesh V. Puthen (14778610) (author), Karsten Suhre (67967) (author), Zohreh Tatari (14778613) (author), Ammira A. Akil (19326085) (author), Tawfeg Ben-Omran (6663634) (author)
منشور في: 2024
الموضوعات:
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_version_ 1864513540447010816
author Geethanjali Devadoss Gandhi (14780425)
author2 Elbay Aliyev (14056972)
Najeeb Syed (12561967)
Fazulur Rehaman Vempalli (14778577)
Chadi Saad (5369351)
Hamdi Mbarek (134997)
Omayma Al-Saei (18288931)
Aljazi Al-Maraghi (14056975)
Mona Abdi (10196665)
Navaneethakrishnan Krishnamoorthy (391608)
Ramin Badii (491543)
Said I. Ismail (11721428)
Wadha Al-Muftah (14152551)
Radja Badji (14152548)
Dima Darwish (14152545)
Tasnim Fadl (14152533)
Heba Yasin (14152542)
Maryem Ennaifar (14778556)
Rania Abdellatif (18589450)
Fatima Alkuwari (14778562)
Muhammad Alvi (4831311)
Yasser Al-Sarraj (11721425)
Asmaa Althani (499903)
Eleni Fethnou (14778568)
Fatima Qafoud (14778571)
Eiman Alkhayat (14778574)
Nahla Afifi (193245)
Sara Tomei (3441323)
Wei Liu (20030)
Stephan Lorenz (466378)
Hakeem Almabrazi (6561371)
Ramzi Temanni (671528)
Tariq Abu Saqri (14778580)
Mohammedhusen Khatib (14778583)
Mehshad Hamza (14778586)
Tariq Abu Zaid (14778589)
Ahmed El Khouly (14778592)
Tushar Pathare (14778595)
Shafeeq Poolat (14778598)
Rashid Al-Ali (846229)
Omar Albagha (8977856)
Souhaila Al-Khodor (247417)
Mashael Alshafai (14778607)
Lotfi Chouchane (61840)
Xavier Estivill (23803)
Khalid A. Fakhro (3158862)
Younes Mokrab (6367)
Jithesh V. Puthen (14778610)
Karsten Suhre (67967)
Zohreh Tatari (14778613)
Ammira A. Akil (19326085)
Tawfeg Ben-Omran (6663634)
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author_facet Geethanjali Devadoss Gandhi (14780425)
Elbay Aliyev (14056972)
Najeeb Syed (12561967)
Fazulur Rehaman Vempalli (14778577)
Chadi Saad (5369351)
Hamdi Mbarek (134997)
Omayma Al-Saei (18288931)
Aljazi Al-Maraghi (14056975)
Mona Abdi (10196665)
Navaneethakrishnan Krishnamoorthy (391608)
Ramin Badii (491543)
Said I. Ismail (11721428)
Wadha Al-Muftah (14152551)
Radja Badji (14152548)
Dima Darwish (14152545)
Tasnim Fadl (14152533)
Heba Yasin (14152542)
Maryem Ennaifar (14778556)
Rania Abdellatif (18589450)
Fatima Alkuwari (14778562)
Muhammad Alvi (4831311)
Yasser Al-Sarraj (11721425)
Asmaa Althani (499903)
Eleni Fethnou (14778568)
Fatima Qafoud (14778571)
Eiman Alkhayat (14778574)
Nahla Afifi (193245)
Sara Tomei (3441323)
Wei Liu (20030)
Stephan Lorenz (466378)
Hakeem Almabrazi (6561371)
Ramzi Temanni (671528)
Tariq Abu Saqri (14778580)
Mohammedhusen Khatib (14778583)
Mehshad Hamza (14778586)
Tariq Abu Zaid (14778589)
Ahmed El Khouly (14778592)
Tushar Pathare (14778595)
Shafeeq Poolat (14778598)
Rashid Al-Ali (846229)
Omar Albagha (8977856)
Souhaila Al-Khodor (247417)
Mashael Alshafai (14778607)
Lotfi Chouchane (61840)
Xavier Estivill (23803)
Khalid A. Fakhro (3158862)
Younes Mokrab (6367)
Jithesh V. Puthen (14778610)
Karsten Suhre (67967)
Zohreh Tatari (14778613)
Ammira A. Akil (19326085)
Tawfeg Ben-Omran (6663634)
author_role author
dc.creator.none.fl_str_mv Geethanjali Devadoss Gandhi (14780425)
Elbay Aliyev (14056972)
Najeeb Syed (12561967)
Fazulur Rehaman Vempalli (14778577)
Chadi Saad (5369351)
Hamdi Mbarek (134997)
Omayma Al-Saei (18288931)
Aljazi Al-Maraghi (14056975)
Mona Abdi (10196665)
Navaneethakrishnan Krishnamoorthy (391608)
Ramin Badii (491543)
Said I. Ismail (11721428)
Wadha Al-Muftah (14152551)
Radja Badji (14152548)
Dima Darwish (14152545)
Tasnim Fadl (14152533)
Heba Yasin (14152542)
Maryem Ennaifar (14778556)
Rania Abdellatif (18589450)
Fatima Alkuwari (14778562)
Muhammad Alvi (4831311)
Yasser Al-Sarraj (11721425)
Asmaa Althani (499903)
Eleni Fethnou (14778568)
Fatima Qafoud (14778571)
Eiman Alkhayat (14778574)
Nahla Afifi (193245)
Sara Tomei (3441323)
Wei Liu (20030)
Stephan Lorenz (466378)
Hakeem Almabrazi (6561371)
Ramzi Temanni (671528)
Tariq Abu Saqri (14778580)
Mohammedhusen Khatib (14778583)
Mehshad Hamza (14778586)
Tariq Abu Zaid (14778589)
Ahmed El Khouly (14778592)
Tushar Pathare (14778595)
Shafeeq Poolat (14778598)
Rashid Al-Ali (846229)
Omar Albagha (8977856)
Souhaila Al-Khodor (247417)
Mashael Alshafai (14778607)
Lotfi Chouchane (61840)
Xavier Estivill (23803)
Khalid A. Fakhro (3158862)
Younes Mokrab (6367)
Jithesh V. Puthen (14778610)
Karsten Suhre (67967)
Zohreh Tatari (14778613)
Ammira A. Akil (19326085)
Tawfeg Ben-Omran (6663634)
dc.date.none.fl_str_mv 2024-10-19T18:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.gim.2024.101268
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Mapping_the_genetic_landscape_of_treatable_inherited_metabolic_disorders_in_a_large_Middle_Eastern_biobank/30024373
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Health sciences
Public health
Carrier frequency
Inbreeding coefficient
Inherited metabolic disorders
Middle Eastern population
VUS reclassification
dc.title.none.fl_str_mv Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Purpose</h3><p dir="ltr">To date, approximately 1400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2% to 3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessive, leading to a potentially higher incidence in regions with high consanguinity. </p><h3>Methodology</h3><p dir="ltr">The study utilized genome sequencing data from 14,060 adult Qatari participants who were recruited by the Qatar Biobank and sequenced by the Qatar Genome Program. The genome sequencing data were analyzed for 125 nuclear genes known to be associated with 115 treatable IMDs. </p><h3>Results</h3><p dir="ltr">Our study identified 253 pathogenic/likely pathogenic single-nucleotide variations associated with 69 treatable IMDs, including 211 known and 42 novel predicted loss-of-function variants. We estimated that approximately 1 in 13 unrelated individuals (8%) carry a heterozygous pathogenic variant for at least 1 of 46 treatable IMDs. Notably, phenylketonuria/hyperphenylalaninemia and homocystinuria had among the highest carrier frequencies (1 in 68 and 1 in 85, respectively). </p><h3>Conclusion</h3><p dir="ltr">Population-based studies of treatable IMDs, particularly in globally under-studied populations, can identify high-frequency alleles segregating in the community and inform public health policies, including carrier and newborn screening.</p><h2>Other Information</h2><p dir="ltr">Published in: Genetics in Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.gim.2024.101268" target="_blank">https://dx.doi.org/10.1016/j.gim.2024.101268</a></p>
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identifier_str_mv 10.1016/j.gim.2024.101268
network_acronym_str Manara2
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spelling Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobankGeethanjali Devadoss Gandhi (14780425)Elbay Aliyev (14056972)Najeeb Syed (12561967)Fazulur Rehaman Vempalli (14778577)Chadi Saad (5369351)Hamdi Mbarek (134997)Omayma Al-Saei (18288931)Aljazi Al-Maraghi (14056975)Mona Abdi (10196665)Navaneethakrishnan Krishnamoorthy (391608)Ramin Badii (491543)Said I. Ismail (11721428)Wadha Al-Muftah (14152551)Radja Badji (14152548)Dima Darwish (14152545)Tasnim Fadl (14152533)Heba Yasin (14152542)Maryem Ennaifar (14778556)Rania Abdellatif (18589450)Fatima Alkuwari (14778562)Muhammad Alvi (4831311)Yasser Al-Sarraj (11721425)Asmaa Althani (499903)Eleni Fethnou (14778568)Fatima Qafoud (14778571)Eiman Alkhayat (14778574)Nahla Afifi (193245)Sara Tomei (3441323)Wei Liu (20030)Stephan Lorenz (466378)Hakeem Almabrazi (6561371)Ramzi Temanni (671528)Tariq Abu Saqri (14778580)Mohammedhusen Khatib (14778583)Mehshad Hamza (14778586)Tariq Abu Zaid (14778589)Ahmed El Khouly (14778592)Tushar Pathare (14778595)Shafeeq Poolat (14778598)Rashid Al-Ali (846229)Omar Albagha (8977856)Souhaila Al-Khodor (247417)Mashael Alshafai (14778607)Lotfi Chouchane (61840)Xavier Estivill (23803)Khalid A. Fakhro (3158862)Younes Mokrab (6367)Jithesh V. Puthen (14778610)Karsten Suhre (67967)Zohreh Tatari (14778613)Ammira A. Akil (19326085)Tawfeg Ben-Omran (6663634)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesHealth sciencesPublic healthCarrier frequencyInbreeding coefficientInherited metabolic disordersMiddle Eastern populationVUS reclassification<h3>Purpose</h3><p dir="ltr">To date, approximately 1400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2% to 3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessive, leading to a potentially higher incidence in regions with high consanguinity. </p><h3>Methodology</h3><p dir="ltr">The study utilized genome sequencing data from 14,060 adult Qatari participants who were recruited by the Qatar Biobank and sequenced by the Qatar Genome Program. The genome sequencing data were analyzed for 125 nuclear genes known to be associated with 115 treatable IMDs. </p><h3>Results</h3><p dir="ltr">Our study identified 253 pathogenic/likely pathogenic single-nucleotide variations associated with 69 treatable IMDs, including 211 known and 42 novel predicted loss-of-function variants. We estimated that approximately 1 in 13 unrelated individuals (8%) carry a heterozygous pathogenic variant for at least 1 of 46 treatable IMDs. Notably, phenylketonuria/hyperphenylalaninemia and homocystinuria had among the highest carrier frequencies (1 in 68 and 1 in 85, respectively). </p><h3>Conclusion</h3><p dir="ltr">Population-based studies of treatable IMDs, particularly in globally under-studied populations, can identify high-frequency alleles segregating in the community and inform public health policies, including carrier and newborn screening.</p><h2>Other Information</h2><p dir="ltr">Published in: Genetics in Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.gim.2024.101268" target="_blank">https://dx.doi.org/10.1016/j.gim.2024.101268</a></p>2024-10-19T18:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.gim.2024.101268https://figshare.com/articles/journal_contribution/Mapping_the_genetic_landscape_of_treatable_inherited_metabolic_disorders_in_a_large_Middle_Eastern_biobank/30024373CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/300243732024-10-19T18:00:00Z
spellingShingle Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
Geethanjali Devadoss Gandhi (14780425)
Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Health sciences
Public health
Carrier frequency
Inbreeding coefficient
Inherited metabolic disorders
Middle Eastern population
VUS reclassification
status_str publishedVersion
title Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
title_full Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
title_fullStr Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
title_full_unstemmed Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
title_short Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
title_sort Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank
topic Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Health sciences
Public health
Carrier frequency
Inbreeding coefficient
Inherited metabolic disorders
Middle Eastern population
VUS reclassification