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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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.
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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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