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Mapping the Genetic Landscape of Human Cells.
Horlbeck, Max A; Xu, Albert; Wang, Min; Bennett, Neal K; Park, Chong Y; Bogdanoff, Derek; Adamson, Britt; Chow, Eric D; Kampmann, Martin; Peterson, Tim R; Nakamura, Ken; Fischbach, Michael A; Weissman, Jonathan S; Gilbert, Luke A.
Afiliación
  • Horlbeck MA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of C
  • Xu A; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of C
  • Wang M; Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
  • Bennett NK; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
  • Park CY; Innovative Genomics Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Bogdanoff D; Center for Advanced Technology, Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Adamson B; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of C
  • Chow ED; Center for Advanced Technology, Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kampmann M; Institute for Neurodegenerative Diseases and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Peterson TR; Department of Internal Medicine, Division of Bone and Mineral Diseases, and Department of Genetics, Institute for Public Health, Washington University School of Medicine, 425 S. Euclid Ave., St. Louis, MO 63110, USA.
  • Nakamura K; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Fischbach MA; Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
  • Weissman JS; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of C
  • Gilbert LA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: luke.gilbert@ucsf.edu.
Cell ; 174(4): 953-967.e22, 2018 08 09.
Article en En | MEDLINE | ID: mdl-30033366
Seminal yeast studies have established the value of comprehensively mapping genetic interactions (GIs) for inferring gene function. Efforts in human cells using focused gene sets underscore the utility of this approach, but the feasibility of generating large-scale, diverse human GI maps remains unresolved. We developed a CRISPR interference platform for large-scale quantitative mapping of human GIs. We systematically perturbed 222,784 gene pairs in two cancer cell lines. The resultant maps cluster functionally related genes, assigning function to poorly characterized genes, including TMEM261, a new electron transport chain component. Individual GIs pinpoint unexpected relationships between pathways, exemplified by a specific cholesterol biosynthesis intermediate whose accumulation induces deoxynucleotide depletion, causing replicative DNA damage and a synthetic-lethal interaction with the ATR/9-1-1 DNA repair pathway. Our map provides a broad resource, establishes GI maps as a high-resolution tool for dissecting gene function, and serves as a blueprint for mapping the genetic landscape of human cells.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Biomarcadores / Colesterol / Epistasis Genética / Redes Reguladoras de Genes Límite: Humans Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Biomarcadores / Colesterol / Epistasis Genética / Redes Reguladoras de Genes Límite: Humans Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article