Rare variants contribute disproportionately to quantitative trait variation in yeast.

Content Provider	Europe PMC
Author	Bloom, Joshua S Boocock, James Treusch, Sebastian Sadhu, Meru J Day, Laura Oates-Barker, Holly Kruglyak, Leonid
Editor	Landry, Christian R Barkai, Naama
Copyright Year	2019
Abstract	How variants with different frequencies contribute to trait variation is a central question in genetics. We use a unique model system to disentangle the contributions of common and rare variants to quantitative traits. We generated ~14,000 progeny from crosses among 16 diverse yeast strains and identified thousands of quantitative trait loci (QTLs) for 38 traits. We combined our results with sequencing data for 1011 yeast isolates to show that rare variants make a disproportionate contribution to trait variation. Evolutionary analyses revealed that this contribution is driven by rare variants that arose recently, and that negative selection has shaped the relationship between variant frequency and effect size. We leveraged the structure of the crosses to resolve hundreds of QTLs to single genes. These results refine our understanding of trait variation at the population level and suggest that studies of rare variants are a fertile ground for discovery of genetic effects.
Journal	eLife
Volume Number	8
PubMed Central reference number	PMC6892613
PubMed reference number	31647408
e-ISSN	2050084X
DOI	10.7554/elife.49212
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2019-10-24
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. © 2019, Bloom et al
Subject Keyword	complex traits rare variants QTL genetic architecture S. cerevisiae
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Neuroscience Medicine Biochemistry, Genetics and Molecular Biology