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Dissecting the architecture of a quantitative trait locus in yeast

Author

Listed:
  • Lars M. Steinmetz

    (Stanford University School of Medicine
    Stanford Genome Technology Center)

  • Himanshu Sinha

    (Duke University Medical Center)

  • Dan R. Richards

    (Stanford University School of Medicine)

  • Jamie I. Spiegelman

    (Stanford Genome Technology Center)

  • Peter J. Oefner

    (Stanford University School of Medicine
    Stanford Genome Technology Center)

  • John H. McCusker

    (Duke University Medical Center)

  • Ronald W. Davis

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford Genome Technology Center)

Abstract

Most phenotypic diversity in natural populations is characterized by differences in degree rather than in kind. Identification of the actual genes underlying these quantitative traits has proved difficult1,2,3,4,5. As a result, little is known about their genetic architecture. The failures are thought to be due to the different contributions of many underlying genes to the phenotype and the ability of different combinations of genes and environmental factors to produce similar phenotypes6,7. This study combined genome-wide mapping and a new genetic technique named reciprocal-hemizygosity analysis to achieve the complete dissection of a quantitative trait locus (QTL) in Saccharomyces cerevisiae. A QTL architecture was uncovered that was more complex than expected. Functional linkages both in cis and in trans were found between three tightly linked quantitative trait genes that are neither necessary nor sufficient in isolation. This arrangement of alleles explains heterosis (hybrid vigour), the increased fitness of the heterozygote compared with homozygotes. It also demonstrates a deficiency in current approaches to QTL dissection with implications extending to traits in other organisms, including human genetic diseases.

Suggested Citation

  • Lars M. Steinmetz & Himanshu Sinha & Dan R. Richards & Jamie I. Spiegelman & Peter J. Oefner & John H. McCusker & Ronald W. Davis, 2002. "Dissecting the architecture of a quantitative trait locus in yeast," Nature, Nature, vol. 416(6878), pages 326-330, March.
    • Handle: RePEc:nat:nature:v:416:y:2002:i:6878:d:10.1038_416326a
    DOI: 10.1038/416326a
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    Cited by:

    1. Carole Camarasa & Isabelle Sanchez & Pascale Brial & Frédéric Bigey & Sylvie Dequin, 2011. "Phenotypic Landscape of Saccharomyces cerevisiae during Wine Fermentation: Evidence for Origin-Dependent Metabolic Traits," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-12, September.
    2. Ulrike Ober & Wen Huang & Michael Magwire & Martin Schlather & Henner Simianer & Trudy F C Mackay, 2015. "Accounting for Genetic Architecture Improves Sequence Based Genomic Prediction for a Drosophila Fitness Trait," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-17, May.
    3. Reda Rawi & Mohamed El Anbari & Halima Bensmail, 2015. "Model Selection Emphasises the Importance of Non-Chromosomal Information in Genetic Studies," PLOS ONE, Public Library of Science, vol. 10(1), pages 1-10, January.

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