The landscape of genetic complexity across 5,700 gene expression traits in yeast
Top Cited Papers
- 19 January 2005
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 102 (5) , 1572-1577
- https://doi.org/10.1073/pnas.0408709102
Abstract
Many studies have identified quantitative trait loci (QTLs) that contribute to continuous variation in heritable traits of interest. However, general principles regarding the distribution of QTL numbers, effect sizes, and combined effects of multiple QTLs remain to be elucidated. Here, we characterize complex genetics underlying inheritance of thousands of transcript levels in a cross between two strains ofSaccharomyces cerevisiae. Most detected QTLs have weak effects, with a median variance explained of 27% for highly heritable transcripts. Despite the high statistical power of the study, no QTLs were detected for 40% of highly heritable transcripts, indicating extensive genetic complexity. Modeling of QTL detection showed that only 3% of highly heritable transcripts are consistent with single-locus inheritance, 17–18% are consistent with control by one or two loci, and half require more than five loci under additive models. Strikingly, analysis of parent and progeny trait distributions showed that a majority of transcripts exhibit transgressive segregation. Sixteen percent of highly heritable transcripts exhibit evidence of interacting loci. Our results will aid design of future QTL mapping studies and may shed light on the evolution of quantitative traits.Keywords
This publication has 51 references indexed in Scilit:
- Epistasis: too often neglected in complex trait studies?Nature Reviews Genetics, 2004
- Genetic analysis of genome-wide variation in human gene expressionNature, 2004
- Quantitative genetic variation: a post-modern viewHuman Molecular Genetics, 2004
- A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pigNature, 2003
- Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factorsNature Genetics, 2003
- Statistical significance for genomewide studiesProceedings of the National Academy of Sciences, 2003
- Sequencing and comparison of yeast species to identify genes and regulatory elementsNature, 2003
- Dissecting the architecture of a quantitative trait locus in yeastNature, 2002
- Analysis of Variance for Gene Expression Microarray DataJournal of Computational Biology, 2000
- Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitusNature Genetics, 2000