High-dimensional single-cell phenotyping reveals extensive haploinsufficiency

Shinsuke Ohnuki; Yoshikazu Ohya

doi:10.1371/journal.pbio.2005130

High-dimensional single-cell phenotyping reveals extensive haploinsufficiency

PLoS Biol. 2018 May 16;16(5):e2005130. doi: 10.1371/journal.pbio.2005130. eCollection 2018 May.

Authors

Shinsuke Ohnuki¹, Yoshikazu Ohya^{1

2}

Affiliations

¹ Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan.
² AIST-UTokyo Advanced Operando-Measurement Technology Open Innovation Laboratory (OPERANDO-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Kashiwa, Chiba, Japan.

Abstract

Haploinsufficiency, a dominant phenotype caused by a heterozygous loss-of-function mutation, has been rarely observed. However, high-dimensional single-cell phenotyping of yeast morphological characteristics revealed haploinsufficiency phenotypes for more than half of 1,112 essential genes under optimal growth conditions. Additionally, 40% of the essential genes with no obvious phenotype under optimal growth conditions displayed haploinsufficiency under severe growth conditions. Haploinsufficiency was detected more frequently in essential genes than in nonessential genes. Similar haploinsufficiency phenotypes were observed mostly in mutants with heterozygous deletion of functionally related genes, suggesting that haploinsufficiency phenotypes were caused by functional defects of the genes. A global view of the gene network was presented based on the similarities of the haploinsufficiency phenotypes. Our dataset contains rich information regarding essential gene functions, providing evidence that single-cell phenotyping is a powerful approach, even in the heterozygous condition, for analyzing complex biological systems.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Cell Enlargement
Genes, Essential
Haploinsufficiency*
Heterozygote
Phenotype
Saccharomyces cerevisiae
Single-Cell Analysis / methods*

Grant support

Grants-in-Aid of Research Activity Start-up https://www.jsps.go.jp/english/ (grant number JP26882019) to S.O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Grants-in-Aid of Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan http://www.mext.go.jp/en/ (grant number 24370002 and 15H04402) to Y.O. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.