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Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

Danish Saleheen (), Pradeep Natarajan, Irina M. Armean, Wei Zhao, Asif Rasheed, Sumeet A. Khetarpal, Hong-Hee Won, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Kaitlin E. Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Nadeem Hayyat Mallick, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Khalid Mahmood, Naveeduddin Ahmed, Ron Do, Ronald M. Krauss, Daniel G. MacArthur, Stacey Gabriel, Eric S. Lander, Mark J. Daly, Philippe Frossard, John Danesh, Daniel J. Rader and Sekar Kathiresan ()
Additional contact information
Danish Saleheen: Perelman School of Medicine at the University of Pennsylvania
Pradeep Natarajan: Center for Genomic Medicine, Harvard Medical School
Irina M. Armean: Broad Institute of Harvard and MIT
Wei Zhao: Perelman School of Medicine at the University of Pennsylvania
Asif Rasheed: Center for Non-Communicable Diseases
Sumeet A. Khetarpal: Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania
Hong-Hee Won: Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center
Konrad J. Karczewski: Broad Institute of Harvard and MIT
Anne H. O’Donnell-Luria: Broad Institute of Harvard and MIT
Kaitlin E. Samocha: Broad Institute of Harvard and MIT
Benjamin Weisburd: Broad Institute of Harvard and MIT
Namrata Gupta: Broad Institute of Harvard and MIT
Mozzam Zaidi: Center for Non-Communicable Diseases
Maria Samuel: Center for Non-Communicable Diseases
Atif Imran: Center for Non-Communicable Diseases
Shahid Abbas: Faisalabad Institute of Cardiology
Faisal Majeed: Center for Non-Communicable Diseases
Madiha Ishaq: Center for Non-Communicable Diseases
Saba Akhtar: Center for Non-Communicable Diseases
Kevin Trindade: Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania
Megan Mucksavage: Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania
Nadeem Qamar: National Institute of Cardiovascular Disorders
Khan Shah Zaman: National Institute of Cardiovascular Disorders
Zia Yaqoob: National Institute of Cardiovascular Disorders
Tahir Saghir: National Institute of Cardiovascular Disorders
Syed Nadeem Hasan Rizvi: National Institute of Cardiovascular Disorders
Anis Memon: National Institute of Cardiovascular Disorders
Nadeem Hayyat Mallick: Punjab Institute of Cardiology
Mohammad Ishaq: Karachi Institute of Heart Diseases
Syed Zahed Rasheed: Karachi Institute of Heart Diseases
Fazal-ur-Rehman Memon: Red Crescent Institute of Cardiology
Khalid Mahmood: The Civil Hospital
Naveeduddin Ahmed: Liaquat National Hospital
Ron Do: Icahn School of Medicine at Mount Sinai
Ronald M. Krauss: Children’s Hospital Oakland Research Institute
Daniel G. MacArthur: Broad Institute of Harvard and MIT
Stacey Gabriel: Broad Institute of Harvard and MIT
Eric S. Lander: Broad Institute of Harvard and MIT
Mark J. Daly: Broad Institute of Harvard and MIT
Philippe Frossard: Center for Non-Communicable Diseases
John Danesh: MRC/BHF Cardiovascular Epidemiology Unit, University of Cambridge
Daniel J. Rader: Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania
Sekar Kathiresan: Center for Genomic Medicine, Harvard Medical School

Nature, 2017, vol. 544, issue 7649, 235-239

Abstract: By sequencing the exomes of 10,503 individuals living in Pakistan, the authors identify rare predicted loss-of-function mutations that are estimated to knock out genes and correlate these mutations with a broad range of phenotypes, providing a framework for a human knockout project.

Date: 2017
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DOI: 10.1038/nature22034

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