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Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross

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Abstract

Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F2 intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here we use the increased resolution of the combined F9 and F10 generations (n = 1455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long-bone lengths. Of these, 49 were previously identified in the combined F2-F3 population of this intercross, while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect three to four long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving three F2-F3 QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long-bone length.

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Acknowledgments

The authors gratefully acknowledge the support of National Institutes of Health grant AR053224. EAN is supported by the Monticello College Foundation Olin Fellowship for Women. We thank E. Ann Carson, Mihaela Pavličev, Linda J. Sandell, and two anonymous reviewers for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Washington University School of Medicine, Box 8108, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Elizabeth A. Norgard, Joseph P. Jarvis, Charles C. Roseman, Kaitlin E. Samocha, L. Susan Pletscher, Bing Wang, Gloria L. Fawcett, Christopher J. Leatherwood & James M. Cheverud

  2. Department of Anthropology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Charles C. Roseman

  3. Division of Epidemiology and Disease Control, The University of Texas School of Public Health, Houston, TX, 77225, USA

    Taylor J. Maxwell

  4. Department of Biological Sciences, University of South Carolina, Columbia, SC, 29208, USA

    Jane P. Kenney-Hunt

  5. Faculty of Life Sciences, Manchester University, Manchester, M12 9PT, UK

    Jason B. Wolf

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  1. Elizabeth A. Norgard
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  2. Joseph P. Jarvis
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  3. Charles C. Roseman
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  5. Jane P. Kenney-Hunt
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  7. L. Susan Pletscher
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  8. Bing Wang
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  9. Gloria L. Fawcett
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  10. Christopher J. Leatherwood
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  12. James M. Cheverud
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Correspondence to Elizabeth A. Norgard.

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Norgard, E.A., Jarvis, J.P., Roseman, C.C. et al. Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross. Mamm Genome 20, 224–235 (2009). https://doi.org/10.1007/s00335-009-9174-9

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  • DOI: https://doi.org/10.1007/s00335-009-9174-9

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