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Yeast reciprocal hemizygosity to confirm the causality of a quantitative trait loci-associated gene

Journal article
Authors Jonas Warringer
G. Liti
Anders Blomberg
Published in Cold Spring Harbor Protocols
Issue 8
Pages 636-640
ISSN 1940-3402
Publication year 2017
Published at Department of Chemistry and Molecular Biology
Pages 636-640
Language en
Links doi.org/10.1101/pdb.prot089078
Keywords allele, animal behavior, case report, deletion mutant, diploidy, gene deletion, gene disruption, genome, hemizygote, human, knockout gene, nonhuman, quantitative trait locus, wild type, yeast
Subject categories Chemical Sciences

Abstract

Pinpointing causal alleles within a quantitative trait loci region is a key challenge when dissecting the genetic basis of natural variation. In yeast, homing in on culprit genes is often achieved using engineered reciprocal hemizygotes as outlined here. Based on prior information on gene–trait associations, candidate genes are identified. In haploid versions of both founder strains, a candidate gene is then deleted. Gene knockouts are independently mated to a wild-type version of the other strain, such that two diploid hybrid strains are obtained. These strains are identical with regard to the nuclear genome, except for that they are hemizygotic at the locus of interest and contain different alleles of the candidate gene. If correctly measured, a trait difference between these reciprocal hemizygotes can confidently be ascribed to allelic variation at the target locus. © 2017 Cold Spring Harbor Laboratory Press.

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