Genome-wide association mapping of blood cell traits in mice

• Published in: Mammalian genome Vol. 24; no. 3-4; pp. 105 - 118
• Main Authors: Davis, Richard C, van Nas, Atila, Bennett, Brian, Orozco, Luz, Pan, Calvin, Rau, Christoph D, Eskin, Eleazar, Lusis, Aldons J
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.04.2013; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Blood Cells; Blood Cells - physiology; Cell Biology; Chromosome Mapping; crossing; Erythrocyte Indices; Erythrocyte Indices - genetics; erythrocytes; genes; genetic variation; genetics; Genome-Wide Association Study; Genome-Wide Association Study - methods; Genotype; granulocytes; Human Genetics; humans; hybrids; Leukocyte Count; Life Sciences; Linkage Disequilibrium; loci; lymphocytes; Male; methods; Mice; Mice, Inbred C57BL; monocytes; Mutation; Phenotype; physiology; Polymorphism, Single Nucleotide; Quantitative Trait Loci; single nucleotide polymorphism; Recombinant Inbred Strain; Mean Corpuscular Volume; Mean Corpuscular Hemoglobin Concentration; Linkage Disequilibrium Block; Quantitative Trait Locus
• ISSN: 0938-8990; 1432-1777; 1432-1777
• DOI: 10.1007/s00335-013-9448-0

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.