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Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits

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Abstract

We have developed an association-based approach using classical inbred strains of mice in which we correct for population structure, which is very extensive in mice, using an efficient mixed-model algorithm. Our approach includes inbred parental strains as well as recombinant inbred strains in order to capture loci with effect sizes typical of complex traits in mice (in the range of 5 % of total trait variance). Over the last few years, we have typed the hybrid mouse diversity panel (HMDP) strains for a variety of clinical traits as well as intermediate phenotypes and have shown that the HMDP has sufficient power to map genes for highly complex traits with resolution that is in most cases less than a megabase. In this essay, we review our experience with the HMDP, describe various ongoing projects, and discuss how the HMDP may fit into the larger picture of common diseases and different approaches.

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Acknowledgments

Funding for this work was supported in part by the U.S. National Institutes of Health (NIH) grants NIAMS RO1 AR057759 (CRF) and NHLBI K99 HL102223 (BJB); the Ruth L. Kirschstein National Research Service Awards T32 HL69766 (CDR), T32-HL007895 (JW), NINDS R01 NS050148 and NIGMS R01 GM098273 (DJS), NHLBI RO1 HL098227 (RCL), NIDDK DP3 DK094311 (AJL, RCD, RCL), NIH RO1 GM095656 (MP), NIDDK RO1 DK072206 (TAD), RO1 DK080339 (STH), 5RO1 DC010856-02 (JDO, RAF), PO1 HL028481 (KR), and PO1 HL090553 (KR). EE was supported by National Science Foundation grants 0513612, 0731455, 0729049, 0916676, and 1065276, and NIH grants K25-HL080079, U01 DA024417, P01-HL30568, and PO1-HL28481. LDO was supported by USPHS National Research Service Award GM07104 and USPHS National Research Service Award T32-HG002536. This research was supported in part by the University of California, Los Angeles, CA, subcontract of contract N01-ES-45530 from the National Toxicology Program and National Institute of Environmental Health Sciences to Perlegen Sciences (EE) and from the Russian Program #2011-1.5-501-006-024 (VAK) and NIH RO1 HL105623 (VAK).

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Authors and Affiliations

  1. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Anatole Ghazalpour, Mete Civelek, Richard C. Davis, Simon T. Hui, Brian W. Parks & Aldons J. Lusis

  2. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA

    Christoph D. Rau, James N. Weiss & Aldons J. Lusis

  3. Departments of Medicine and Biochemistry and Molecular Genetics, and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

    Charles R. Farber

  4. Department of Genetics, and Nutrition Research Institute, University of North Carolina, Chapel Hill, NC, USA

    Brian J. Bennett

  5. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Luz D. Orozco, Atila van Nas, Calvin Pan, Jong Wha Joo, Lisa J. Martin, Karen Reue, Jessica Wang, Eleazar Eskin & Aldons J. Lusis

  6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Hooman Allayee

  7. Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Simon W. Beaven

  8. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Thomas A. Drake

  9. Department of Otology/Skull Base Surgery, House Research Institute, Los Angeles, CA, USA

    Rick A. Friedman

  10. Department of Computer Sciences, University of California, Los Angeles, CA, USA

    Nick Furlotte, Emrah Kostem, Eun Yong Kang & Eleazar Eskin

  11. Department of Psychology & Behavioral Neuroscience and Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    J. David Jentsch

  12. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Hyun Min Kang

  13. Bioinformatics Program, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Jong Wha Joo

  14. Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Vyacheslav A. Korshunov

  15. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA

    Rick E. Laughlin

  16. Department of Cell Biology and Genetics, House Research Institute, Los Angeles, CA, USA

    Jeffrey D. Ohmen

  17. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA

    Matteo Pellegrini

  18. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Desmond J. Smith

  19. Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Sotirios Tetradis

  20. Division of Diagnostic and Surgical Science, School of Dentistry, University of California, Los Angeles, CA, USA

    Sotirios Tetradis & Aldons J. Lusis

  21. Department of Medicine/Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Jessica Wang

  22. Division of Molecular Medicine, Department of Anesthesiology, Physiology and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Yibin Wang

  23. Department of Cardiovascular Drug Discovery, Bristol-Myers Squibb Co, Pennington, NJ, USA

    Todd Kirchgessner & Peter S. Gargalovic

  24. Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 850 Republican Street, Seattle, WA, 98109-4725, USA

    Renée C. LeBoeuf

Authors
  1. Anatole Ghazalpour
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  2. Christoph D. Rau
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  3. Charles R. Farber
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  4. Brian J. Bennett
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  5. Luz D. Orozco
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  6. Atila van Nas
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  7. Calvin Pan
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  8. Hooman Allayee
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  9. Simon W. Beaven
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  10. Mete Civelek
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  11. Richard C. Davis
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  12. Thomas A. Drake
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  13. Rick A. Friedman
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  14. Nick Furlotte
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  15. Simon T. Hui
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  16. J. David Jentsch
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  17. Emrah Kostem
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  18. Hyun Min Kang
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  19. Eun Yong Kang
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  20. Jong Wha Joo
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  21. Vyacheslav A. Korshunov
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  22. Rick E. Laughlin
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  23. Lisa J. Martin
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  24. Jeffrey D. Ohmen
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  25. Brian W. Parks
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  26. Matteo Pellegrini
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  27. Karen Reue
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  28. Desmond J. Smith
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  29. Sotirios Tetradis
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  30. Jessica Wang
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  31. Yibin Wang
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  32. James N. Weiss
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  33. Todd Kirchgessner
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  34. Peter S. Gargalovic
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  35. Eleazar Eskin
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  36. Aldons J. Lusis
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  37. Renée C. LeBoeuf
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Corresponding author

Correspondence to Renée C. LeBoeuf.

Additional information

Anatole Ghazalpour, Christoph D. Rau, Charles R. Farber, Brian J. Bennett, Luz D. Orozco, and Atila van Nas contributed equally to this work.

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Ghazalpour, A., Rau, C.D., Farber, C.R. et al. Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits. Mamm Genome 23, 680–692 (2012). https://doi.org/10.1007/s00335-012-9411-5

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