TY - JOUR TI - Rare variants contribute disproportionately to quantitative trait variation in yeast AU - Bloom, Joshua S AU - Boocock, James AU - Treusch, Sebastian AU - Sadhu, Meru J AU - Day, Laura AU - Oates-Barker, Holly AU - Kruglyak, Leonid A2 - Landry, Christian R A2 - Barkai, Naama VL - 8 PY - 2019 DA - 2019/10/24 SP - e49212 C1 - eLife 2019;8:e49212 DO - 10.7554/eLife.49212 UR - https://doi.org/10.7554/eLife.49212 AB - 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. KW - complex traits KW - rare variants KW - QTL KW - genetic architecture JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -