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A large-sample QTL study in mice: I. Growth

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Abstract

By use of long-term selection lines for high and low growth, a large-sample (n = ~1,000 F2) experiment was conducted in mice to further understand the genetic architecture of complex polygenic traits. In combination with previous work, we conclude that QTL analysis has reinforced classic polygenic paradigms put in place prior to molecular analysis. Composite interval mapping revealed large numbers of QTL for growth traits with an exponential distribution of magnitudes of effects and validated theoretical expectations regarding gene action. Of particular significance, large effects were detected on Chromosome (Chr) 2. Regions on Chrs 1, 3, 6, 10, 11, and 17 also harbor loci with significant contributions to phenotypic variation for growth. Despite the large sample size, average confidence intervals of ~20 cM exhibit the poor resolution for initial estimates of QTL location. Analysis with genome-wide and chromosomal polygenic models revealed that, under certain assumptions, large fractions of the genome may contribute little to phenotypic variation for growth. Only a few epistatic interactions among detected QTL, little statistical support for gender-specific QTL, and significant age effects on genetic architecture were other primary observations from this study.

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Acknowledgements

We gratefully acknowledge Mary Ann Cushman, Stephenie Foster, and Grady Beck for collection of genotypic data. We appreciate the assistance of James Specht and Steven Kachman in statistical analyses and use of QTL detection computer packages. We have also benefited greatly from useful discussions with Jerry Taylor, Mark Thallman, and Gary Rohrer, and from constructive reviews of a previous version of this manuscript by Bill Hill and Merlyn Nielsen. J.L. Rocha acknowledges the support of the Portuguese Foundation for Science and Technology. This research is a contribution of the University of Nebraska Agricultural Research Division (Lincoln, nab.; Journal Series No. 14110) and the North Carolina Agricultural Research Service, and was supported in part by funds provided through the Hatch Act. This research was also partially based upon work supported by the National Science Foundation under Grant No. 0091900 (Nebraska EPSCOR infrastructure improvement grant).

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Authors and Affiliations

  1. Department of Animal Science, University of Nebraska, Lincoln, Nebraska 68583-0908, USA

    Joao L. Rocha & Daniel Pomp

  2. Department of Animal Science, North Carolina State University, Raleigh, North Carolina, 27695-7621, USA

    Eugene J. Eisen

  3. ARS, USMARC, USDA, Lincoln, Nebraska 68583-0908, USA

    L. Dale Van Vleck

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  1. Joao L. Rocha
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  2. Eugene J. Eisen
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  3. L. Dale Van Vleck
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  4. Daniel Pomp
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Correspondence to Daniel Pomp.

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Rocha, J.L., Eisen, E.J., Dale Van Vleck, L. et al. A large-sample QTL study in mice: I. Growth . Mamm Genome 15, 83–99 (2004). https://doi.org/10.1007/s00335-003-2312-x

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