The landscape of tolerated genetic variation in humans and primates
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individual...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187174/ https://www.ncbi.nlm.nih.gov/pubmed/37205491 http://dx.doi.org/10.1101/2023.05.01.538953 |
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author | Gao, Hong Hamp, Tobias Ede, Jeffrey Schraiber, Joshua G. McRae, Jeremy Singer-Berk, Moriel Yang, Yanshen Dietrich, Anastasia Fiziev, Petko Kuderna, Lukas Sundaram, Laksshman Wu, Yibing Adhikari, Aashish Field, Yair Chen, Chen Batzoglou, Serafim Aguet, Francois Lemire, Gabrielle Reimers, Rebecca Balick, Daniel Janiak, Mareike C. Kuhlwilm, Martin Orkin, Joseph D. Manu, Shivakumara Valenzuela, Alejandro Bergman, Juraj Rouselle, Marjolaine Silva, Felipe Ennes Agueda, Lidia Blanc, Julie Gut, Marta de Vries, Dorien Goodhead, Ian Harris, R. Alan Raveendran, Muthuswamy Jensen, Axel Chuma, Idriss S. Horvath, Julie Hvilsom, Christina Juan, David Frandsen, Peter de Melo, Fabiano R. Bertuol, Fabricio Byrne, Hazel Sampaio, Iracilda Farias, Izeni do Amaral, João Valsecchi Messias, Mariluce da Silva, Maria N. F. Trivedi, Mihir Rossi, Rogerio Hrbek, Tomas Andriaholinirina, Nicole Rabarivola, Clément J. Zaramody, Alphonse Jolly, Clifford J. Phillips-Conroy, Jane Wilkerson, Gregory Abee, Christian Simmons, Joe H. Fernandez-Duque, Eduardo Kanthaswamy, Sree Shiferaw, Fekadu Wu, Dongdong Zhou, Long Shao, Yong Zhang, Guojie Keyyu, Julius D. Knauf, Sascha Le, Minh D. Lizano, Esther Merker, Stefan Navarro, Arcadi Batallion, Thomas Nadler, Tilo Khor, Chiea Chuen Lee, Jessica Tan, Patrick Lim, Weng Khong Kitchener, Andrew C. Zinner, Dietmar Gut, Ivo Melin, Amanda Guschanski, Katerina Schierup, Mikkel Heide Beck, Robin M. D. Umapathy, Govindhaswamy Roos, Christian Boubli, Jean P. Lek, Monkol Sunyaev, Shamil O’Donnell, Anne Rehm, Heidi Xu, Jinbo Rogers, Jeffrey Marques-Bonet, Tomas Kai-How Farh, Kyle |
author_facet | Gao, Hong Hamp, Tobias Ede, Jeffrey Schraiber, Joshua G. McRae, Jeremy Singer-Berk, Moriel Yang, Yanshen Dietrich, Anastasia Fiziev, Petko Kuderna, Lukas Sundaram, Laksshman Wu, Yibing Adhikari, Aashish Field, Yair Chen, Chen Batzoglou, Serafim Aguet, Francois Lemire, Gabrielle Reimers, Rebecca Balick, Daniel Janiak, Mareike C. Kuhlwilm, Martin Orkin, Joseph D. Manu, Shivakumara Valenzuela, Alejandro Bergman, Juraj Rouselle, Marjolaine Silva, Felipe Ennes Agueda, Lidia Blanc, Julie Gut, Marta de Vries, Dorien Goodhead, Ian Harris, R. Alan Raveendran, Muthuswamy Jensen, Axel Chuma, Idriss S. Horvath, Julie Hvilsom, Christina Juan, David Frandsen, Peter de Melo, Fabiano R. Bertuol, Fabricio Byrne, Hazel Sampaio, Iracilda Farias, Izeni do Amaral, João Valsecchi Messias, Mariluce da Silva, Maria N. F. Trivedi, Mihir Rossi, Rogerio Hrbek, Tomas Andriaholinirina, Nicole Rabarivola, Clément J. Zaramody, Alphonse Jolly, Clifford J. Phillips-Conroy, Jane Wilkerson, Gregory Abee, Christian Simmons, Joe H. Fernandez-Duque, Eduardo Kanthaswamy, Sree Shiferaw, Fekadu Wu, Dongdong Zhou, Long Shao, Yong Zhang, Guojie Keyyu, Julius D. Knauf, Sascha Le, Minh D. Lizano, Esther Merker, Stefan Navarro, Arcadi Batallion, Thomas Nadler, Tilo Khor, Chiea Chuen Lee, Jessica Tan, Patrick Lim, Weng Khong Kitchener, Andrew C. Zinner, Dietmar Gut, Ivo Melin, Amanda Guschanski, Katerina Schierup, Mikkel Heide Beck, Robin M. D. Umapathy, Govindhaswamy Roos, Christian Boubli, Jean P. Lek, Monkol Sunyaev, Shamil O’Donnell, Anne Rehm, Heidi Xu, Jinbo Rogers, Jeffrey Marques-Bonet, Tomas Kai-How Farh, Kyle |
author_sort | Gao, Hong |
collection | PubMed |
description | Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. |
format | Online Article Text |
id | pubmed-10187174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-101871742023-05-17 The landscape of tolerated genetic variation in humans and primates Gao, Hong Hamp, Tobias Ede, Jeffrey Schraiber, Joshua G. McRae, Jeremy Singer-Berk, Moriel Yang, Yanshen Dietrich, Anastasia Fiziev, Petko Kuderna, Lukas Sundaram, Laksshman Wu, Yibing Adhikari, Aashish Field, Yair Chen, Chen Batzoglou, Serafim Aguet, Francois Lemire, Gabrielle Reimers, Rebecca Balick, Daniel Janiak, Mareike C. Kuhlwilm, Martin Orkin, Joseph D. Manu, Shivakumara Valenzuela, Alejandro Bergman, Juraj Rouselle, Marjolaine Silva, Felipe Ennes Agueda, Lidia Blanc, Julie Gut, Marta de Vries, Dorien Goodhead, Ian Harris, R. Alan Raveendran, Muthuswamy Jensen, Axel Chuma, Idriss S. Horvath, Julie Hvilsom, Christina Juan, David Frandsen, Peter de Melo, Fabiano R. Bertuol, Fabricio Byrne, Hazel Sampaio, Iracilda Farias, Izeni do Amaral, João Valsecchi Messias, Mariluce da Silva, Maria N. F. Trivedi, Mihir Rossi, Rogerio Hrbek, Tomas Andriaholinirina, Nicole Rabarivola, Clément J. Zaramody, Alphonse Jolly, Clifford J. Phillips-Conroy, Jane Wilkerson, Gregory Abee, Christian Simmons, Joe H. Fernandez-Duque, Eduardo Kanthaswamy, Sree Shiferaw, Fekadu Wu, Dongdong Zhou, Long Shao, Yong Zhang, Guojie Keyyu, Julius D. Knauf, Sascha Le, Minh D. Lizano, Esther Merker, Stefan Navarro, Arcadi Batallion, Thomas Nadler, Tilo Khor, Chiea Chuen Lee, Jessica Tan, Patrick Lim, Weng Khong Kitchener, Andrew C. Zinner, Dietmar Gut, Ivo Melin, Amanda Guschanski, Katerina Schierup, Mikkel Heide Beck, Robin M. D. Umapathy, Govindhaswamy Roos, Christian Boubli, Jean P. Lek, Monkol Sunyaev, Shamil O’Donnell, Anne Rehm, Heidi Xu, Jinbo Rogers, Jeffrey Marques-Bonet, Tomas Kai-How Farh, Kyle bioRxiv Article Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. Cold Spring Harbor Laboratory 2023-05-02 /pmc/articles/PMC10187174/ /pubmed/37205491 http://dx.doi.org/10.1101/2023.05.01.538953 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Gao, Hong Hamp, Tobias Ede, Jeffrey Schraiber, Joshua G. McRae, Jeremy Singer-Berk, Moriel Yang, Yanshen Dietrich, Anastasia Fiziev, Petko Kuderna, Lukas Sundaram, Laksshman Wu, Yibing Adhikari, Aashish Field, Yair Chen, Chen Batzoglou, Serafim Aguet, Francois Lemire, Gabrielle Reimers, Rebecca Balick, Daniel Janiak, Mareike C. Kuhlwilm, Martin Orkin, Joseph D. Manu, Shivakumara Valenzuela, Alejandro Bergman, Juraj Rouselle, Marjolaine Silva, Felipe Ennes Agueda, Lidia Blanc, Julie Gut, Marta de Vries, Dorien Goodhead, Ian Harris, R. Alan Raveendran, Muthuswamy Jensen, Axel Chuma, Idriss S. Horvath, Julie Hvilsom, Christina Juan, David Frandsen, Peter de Melo, Fabiano R. Bertuol, Fabricio Byrne, Hazel Sampaio, Iracilda Farias, Izeni do Amaral, João Valsecchi Messias, Mariluce da Silva, Maria N. F. Trivedi, Mihir Rossi, Rogerio Hrbek, Tomas Andriaholinirina, Nicole Rabarivola, Clément J. Zaramody, Alphonse Jolly, Clifford J. Phillips-Conroy, Jane Wilkerson, Gregory Abee, Christian Simmons, Joe H. Fernandez-Duque, Eduardo Kanthaswamy, Sree Shiferaw, Fekadu Wu, Dongdong Zhou, Long Shao, Yong Zhang, Guojie Keyyu, Julius D. Knauf, Sascha Le, Minh D. Lizano, Esther Merker, Stefan Navarro, Arcadi Batallion, Thomas Nadler, Tilo Khor, Chiea Chuen Lee, Jessica Tan, Patrick Lim, Weng Khong Kitchener, Andrew C. Zinner, Dietmar Gut, Ivo Melin, Amanda Guschanski, Katerina Schierup, Mikkel Heide Beck, Robin M. D. Umapathy, Govindhaswamy Roos, Christian Boubli, Jean P. Lek, Monkol Sunyaev, Shamil O’Donnell, Anne Rehm, Heidi Xu, Jinbo Rogers, Jeffrey Marques-Bonet, Tomas Kai-How Farh, Kyle The landscape of tolerated genetic variation in humans and primates |
title | The landscape of tolerated genetic variation in humans and primates |
title_full | The landscape of tolerated genetic variation in humans and primates |
title_fullStr | The landscape of tolerated genetic variation in humans and primates |
title_full_unstemmed | The landscape of tolerated genetic variation in humans and primates |
title_short | The landscape of tolerated genetic variation in humans and primates |
title_sort | landscape of tolerated genetic variation in humans and primates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187174/ https://www.ncbi.nlm.nih.gov/pubmed/37205491 http://dx.doi.org/10.1101/2023.05.01.538953 |
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