Quantitative trait loci analysis for peripheral blood parameters in a (BALB/cW × C57BL/6J-Mpl (hlb219)/J) F(2) mice

Abstract

The genetic basis of the peripheral blood cell parameters is not fully elucidated. Thus, it is essential to research the correlation between blood cell counts levels and the genome in laboratory animals and subsequently in humans. In the present study, we examined 288 F(2) mice from a cross between BALB/cW and C57BL/6J-Mpl(hlb219)/J. The C57BL/6J-Mpl (hlb219)/J strain is a mouse model of thrombocytopenia. We found very strong correlations for PLT counts and revealed some highly significant correlations for RBC counts. On the basis of the obtained results, we presume that genetic control of erythrocyte parameters is divided into two pathways: first, the morphological determinants responsible for the red blood cell count (RBC), hematocrit (HCT), and mean corpuscular volume (MCV), and second, the functional pathway determining the hemoglobin content (HGB). The locus on Chromosome 4 is the only detected quantitative trait locus (QTL) influencing the analyzed platelets parameters. We also detected highly significant correlations for erythrocyte parameters on Chromosome 1 (RBC, MCV, MCH), Chr 7 (HGB), Chr 9 (MCHC), Chr 11 (RBC), and Chr 17 (MCH). Finally, with regards to the given correlations, using the Mouse Genome Database resource, we proposed candidate genes with possible meaning for the level of these parameters: cytokine receptor genes (e.g., Mpl), transcription factor genes (e.g., Xbp1, Ikzf1), hemoglobin chain genes (e.g., Hbb-b1, Hbb-ar), and many others localized in the confidence intervals of found QTLs.