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Revealing the genetic structure of a trait by sequencing a population under selection

Parts, Leopold; Cubillos, Francisco A.; Warringer, Jonas; Jain, Kanika; Salinas, Francisco; Bumpstead, Suzannah J.; Molin, Mikael; Zia, Amin; Simpson, Jared T.; Quail, Michael A.; Moses, Alan; Louis, Edward J.; Durbin, Richard; Liti, Gianni

Authors

Leopold Parts

Francisco A. Cubillos

Jonas Warringer

Kanika Jain

Francisco Salinas

Suzannah J. Bumpstead

Mikael Molin

Amin Zia

Jared T. Simpson

Michael A. Quail

Alan Moses

Edward J. Louis

Richard Durbin

Gianni Liti



Abstract

One approach to understanding the genetic basis of traits is to study their pattern of inheritance among offspring of phenotypically different parents. Previously, such analysis has been limited by low mapping resolution, high labor costs, and large sample size requirements for detecting modest effects. Here, we present a novel approach to map trait loci using artificial selection. First, we generated populations of 10–100 million haploid and diploid segregants by crossing two budding yeast strains of different heat tolerance for up to 12 generations. We then subjected these large segregant pools to heat stress for up to 12 d, enriching for beneficial alleles. Finally, we sequenced total DNA from the pools before and during selection to measure the changes in parental allele frequency. We mapped 21 intervals with significant changes in genetic background in response to selection, which is several times more than found with traditional linkage methods. Nine of these regions contained two or fewer genes, yielding much higher resolution than previous genomic linkage studies. Multiple members of the RAS/cAMP signaling pathway were implicated, along with genes previously not annotated with heat stress response function. Surprisingly, at most selected loci, allele frequencies stopped changing before the end of the selection experiment, but alleles did not become fixed. Furthermore, we were able to detect the same set of trait loci in a population of diploid individuals with similar power and resolution, and observed primarily additive effects, similar to what is seen for complex trait genetics in other diploid organisms such as humans.

Citation

Parts, L., Cubillos, F. A., Warringer, J., Jain, K., Salinas, F., Bumpstead, S. J., …Liti, G. (2011). Revealing the genetic structure of a trait by sequencing a population under selection. Genome Research, 21(7), doi:10.1101/gr.116731.110

Journal Article Type Article
Publication Date Jul 1, 2011
Deposit Date Apr 4, 2014
Publicly Available Date Apr 4, 2014
Journal Genome Research
Print ISSN 1088-9051
Electronic ISSN 1088-9051
Publisher Cold Spring Harbor Laboratory Press
Peer Reviewed Peer Reviewed
Volume 21
Issue 7
DOI https://doi.org/10.1101/gr.116731.110
Public URL http://eprints.nottingham.ac.uk/id/eprint/2866
Publisher URL http://genome.cshlp.org/content/21/7/1131.abstract?sid=14fbe38f-eecd-44e7-86bf-b6f16952e2de
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0



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