Rare variants contribute disproportionately to quantitative trait variation in yeast.
Elife
; 82019 10 24.
Article
in En
| MEDLINE
| ID: mdl-31647408
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
/
Genetic Variation
/
Genome, Fungal
/
Quantitative Trait, Heritable
/
Quantitative Trait Loci
Type of study:
Prognostic_studies
Language:
En
Journal:
Elife
Year:
2019
Type:
Article
Affiliation country:
United States