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

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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Correspondence to Renée C. LeBoeuf.

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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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  • DOI: https://doi.org/10.1007/s00335-012-9411-5

Keywords

  • Bone Mineral Density
  • Inbred Strain
  • Coexpression Network
  • Recombinant Inbred
  • Linkage Disequilibrium Block