Characterization and prediction of haploinsufficiency using systems-level gene properties in yeast

G3 (Bethesda). 2013 Nov 6;3(11):1965-77. doi: 10.1534/g3.113.008144.

Abstract

Variation in gene copy number can significantly affect organism fitness. When one allele is missing in a diploid, the phenotype can be compromised because of haploinsufficiency. In this work, we identified associations between Saccharomyces cerevisiae gene properties and genome-scale haploinsufficiency phenotypes from previous work. We compared the haploinsufficiency profiles against 23 gene properties and found that genes with higher level of connectivity (degree) in a protein-protein interaction network, higher genetic interaction degree, greater gene sequence conservation, and higher protein expression were significantly more likely to be haploinsufficient. Additionally, haploinsufficiency showed negative relationships with cell cycle regulation and promoter sequence conservation.

Keywords: correlation; genome; haploinsufficiency; machine-learning; prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Gene Regulatory Networks
  • Genome, Fungal*
  • Haploinsufficiency / genetics*
  • Open Reading Frames / genetics
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Interaction Maps / genetics
  • RNA, Messenger / metabolism
  • ROC Curve
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / genetics

Substances

  • Cell Cycle Proteins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins