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Genome-wide association mapping of blood cell traits in mice

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Abstract

Genetic variations in blood cell parameters can impact clinical traits. We report here the mapping of blood cell traits in a panel of 100 inbred strains of mice of the Hybrid Mouse Diversity Panel (HMDP) using genome-wide association (GWA). We replicated a locus previously identified in using linkage analysis in several genetic crosses for mean corpuscular volume (MCV) and a number of other red blood cell traits on distal chromosome 7. Our peak for SNP association to MCV occurred in a linkage disequilibrium (LD) block spanning from 109.38 to 111.75 Mb that includes Hbb-b1, the likely causal gene. Altogether, we identified five loci controlling red blood cell traits (on chromosomes 1, 7, 11, 12, and 16), and four of these correspond to loci for red blood cell traits reported in a recent human GWA study. For white blood cells, including granulocytes, monocytes, and lymphocytes, a total of six significant loci were identified on chromosomes 1, 6, 8, 11, 12, and 15. An average of ten candidate genes were found at each locus and those were prioritized by examining functional variants in the HMDP such as missense and expression variants. These results provide intermediate phenotypes and candidate loci for genetic studies of atherosclerosis and cancer as well as inflammatory and immune disorders in mice.

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Acknowledgments

This work was supported by NIH grants HL030568, HL028841, DK094311.

Disclosures

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

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

    Atila van Nas, Luz Orozco, Calvin Pan, Eleazar Eskin & Aldons J. Lusis

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

    Richard C. Davis, Atila van Nas, Brian Bennett, Luz Orozco & Aldons J. Lusis

  3. Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Christoph D. Rau & Aldons J. Lusis

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

    Aldons J. Lusis

  5. Department of Computer Science, University of California, Los Angeles, CA, USA

    Eleazar Eskin

  6. Med-Cardio/Microbio, University of California, 3730 MRL, P.O. Box 951679, Los Angeles, CA, 90095-1679, USA

    Aldons J. Lusis

Authors
  1. Richard C. Davis
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  2. Atila van Nas
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  3. Brian Bennett
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  4. Luz Orozco
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  5. Calvin Pan
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  6. Christoph D. Rau
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  7. Eleazar Eskin
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  8. Aldons J. Lusis
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Corresponding author

Correspondence to Aldons J. Lusis.

Additional information

van Nas and R. C. Davis contributed equally to this study.

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Davis, R.C., van Nas, A., Bennett, B. et al. Genome-wide association mapping of blood cell traits in mice. Mamm Genome 24, 105–118 (2013). https://doi.org/10.1007/s00335-013-9448-0

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  • DOI: https://doi.org/10.1007/s00335-013-9448-0

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