High-dimensional single-cell phenotyping reveals extensive haploinsufficiency

PLoS Biology
Shinsuke Ohnuki, Yoshikazu Ohya

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.

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Citations

Feb 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Georg OberhoferBruce A Hay
Jul 7, 2019·Nature Protocols·Akihiro IsozakiKeisuke Goda
Sep 25, 2019·Genome Research·Samuel M LancasterMaitreya J Dunham
Mar 7, 2020·Nature Communications·Hideharu MikamiKeisuke Goda
May 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·Summer A Morrill, Angelika Amon
Jan 2, 2020·Journal of Fungi·Shen-Huan Liang, Richard J Bennett
Dec 23, 2020·Microbial Biotechnology·Nobuo FukudaTsutomu Nakamura
Mar 24, 2021·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Thiago CorrêaMariluce Riegel
Dec 10, 2021·PLoS Genetics·M Felicia Basilicata, Claudia Isabelle Keller Valsecchi

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Methods Mentioned

BETA
PCA

Software Mentioned

R
brglm
qvalue
CalMorph
AxioVision
lmtest
gamlss

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