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Genome-wide association mapping of blood cell traits in mice |
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| Authors: | Richard C. Davis Atila van Nas Brian Bennett Luz Orozco Calvin Pan Christoph D. Rau Eleazar Eskin Aldons J. Lusis |
| Affiliation: | 2. Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA 1. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA 3. Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA 5. Department of Computer Science, University of California, Los Angeles, CA, USA 4. Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA 6. Med-Cardio/Microbio, University of California, 3730 MRL, P.O. Box 951679, Los Angeles, CA, 90095-1679, USA |
| 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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