Gene essentiality and synthetic lethality in haploid human cells

Science. 2015 Nov 27;350(6264):1092-6. doi: 10.1126/science.aac7557. Epub 2015 Oct 15.


Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase β adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Regulatory Networks*
  • Genes, Essential*
  • Genes, Lethal*
  • Genetic Fitness / genetics*
  • Golgi Apparatus / genetics
  • Haploidy*
  • Hexosyltransferases / genetics
  • Humans
  • Membrane Proteins / genetics
  • Mutagenesis, Insertional
  • Mutation
  • Saccharomyces cerevisiae / genetics


  • Membrane Proteins
  • Hexosyltransferases
  • dolichyl-diphosphooligosaccharide - protein glycotransferase

Associated data

  • SRA/SRP058962