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Systematic screen for human disease genes in yeast

Systematic screen for human disease genes in yeast High similarity between yeast and human mitochondria allows functional genomic study of Saccharomyces cerevisiae to be used to identify human genes involved in disease 1 . So far, 102 heritable disorders have been attributed to defects in a quarter of the known nuclear-encoded mitochondrial proteins in humans 2 . Many mitochondrial diseases remain unexplained, however, in part because only 40–60% of the presumed 700–1,000 proteins involved in mitochondrial function and biogenesis have been identified 3 . Here we apply a systematic functional screen using the pre-existing whole-genome pool of yeast deletion mutants 4,5,6 to identify mitochondrial proteins. Three million measurements of strain fitness identified 466 genes whose deletions impaired mitochondrial respiration, of which 265 were new. Our approach gave higher selection than other systematic approaches, including fivefold greater selection than gene expression analysis. To apply these advantages to human disorders involving mitochondria, human orthologs were identified and linked to heritable diseases using genomic map positions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Genetics Springer Journals

Systematic screen for human disease genes in yeast

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References (30)

Publisher
Springer Journals
Copyright
Copyright © 2002 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1061-4036
eISSN
1546-1718
DOI
10.1038/ng929
Publisher site
See Article on Publisher Site

Abstract

High similarity between yeast and human mitochondria allows functional genomic study of Saccharomyces cerevisiae to be used to identify human genes involved in disease 1 . So far, 102 heritable disorders have been attributed to defects in a quarter of the known nuclear-encoded mitochondrial proteins in humans 2 . Many mitochondrial diseases remain unexplained, however, in part because only 40–60% of the presumed 700–1,000 proteins involved in mitochondrial function and biogenesis have been identified 3 . Here we apply a systematic functional screen using the pre-existing whole-genome pool of yeast deletion mutants 4,5,6 to identify mitochondrial proteins. Three million measurements of strain fitness identified 466 genes whose deletions impaired mitochondrial respiration, of which 265 were new. Our approach gave higher selection than other systematic approaches, including fivefold greater selection than gene expression analysis. To apply these advantages to human disorders involving mitochondria, human orthologs were identified and linked to heritable diseases using genomic map positions.

Journal

Nature Genetics – Springer Journals

Published: Jul 22, 2002

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