Mcvq12^SM/J
QTL Variant Detail

Summary

• QTL variant: Mcvq12^SM/J
• Name: mean red cell volume QTL 12; SM/J
• MGI ID: MGI:5812354
• QTL: Mcvq12 Location: unknown Genetic Position: Chr12, Syntenic

Variant origin

• Strain of Specimen: SM/J

Variant description

• Allele Type: QTL

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:182607

Blood cells perform an integral role in critical physiological processes from oxygen transport to blood clotting and assorted aspects of infection and immunity. To identify the genetic determinants of red cell parameters, genome-wide association analysis was performed on (LG/J SM/J) F2 and F34 advanced intercross lines using single nucleotide polymorphism genotyping and a novel algorithm for mapping in the combined populations.

To identify candidate genes within QTL mouse genome, expression, published data and LG/J and SM/J genomic sequences were used with a focus on genes with non-synonymous coding SNPs.

LG/J and SM/J mice have been used effectively in studies on a variety of physiologic and

pathophysiologic processes including body weight, diabetes, lipid metabolism, wound

healing and obesity. This study may be one of the first to use these strains and

the first to use AILs to investigate genetic determinants of red blood cell parameters. These strains were also chosen given the known parental genotypes and phenotypes.

462 (LG/J xSM/J) F2 mice (230 females, 232 males) were generated from F1 mice bred from inbred male SM/J and female LG/J mice. 472 F34 mice (231 females, 241 males) were generated from 119 F33 mice of known pedigree back to the original founders.

All mice were involved in a behavioral study after which anticoagulated whole blood was harvested by retro-orbital bleed at 13-14.5 weeks and analyzed by complete blood counts (CBC) to measure several quantitative traits representative of red cell physiology and metabolism, within 48 hours.

F2 and F34 mice were genotyped for 162 and ~4000 evenly-spaced SNPs respectively using the R package QTLRel that accounted for complex relationships among F34 mice.

[Sup Table 1] Using genotype and complete blood count (CBC) data from the F2 and F34 mice significant QTLs were detected for:

mean corpuscular hemoglobin levels (MCH)

mean corpuscular volumes (MCV),

hemoglobin levels (HGB),

red blood cell counts (RBC)

and mean corpuscular hemoglobin concentrations (MCHC)

on chromosomes 6, 7, 8, 10, 12 and 17:

On Chromosome 12 a QTL influencing mean corpuscular hemoglobin was detected mapping between 0.0 and 40.9 Mb with a LOD score of 4.2 in the F2 analysis. This QTL was resolved into four individual QTL in the analysis of the combined F2 and F34 data:

Mchq11 (mean corpuscular hemoglobin QTL 11) mapped between 4.2 and 8.9 Mb (0.0-1.6 cM) on Chr 12 with a LOD score of 6.4.

Mchq12 (mean corpuscular hemoglobin QTL 12) mapped between 9.8 and 12.9 Mb (2.0-4.5 cM) on Chr 12 with a LOD score of 5.5.

Mchq13 (mean corpuscular hemoglobin QTL 13) mapped between 15.8 and 17.0 Mb (5.1-5.6 cM) on Chr 12 with a LOD score of 5.3.

Mchq14 (mean corpuscular hemoglobin QTL 14) mapped between 25.3 and 29.9 Mb (6.7-8.8 cM) on Chr 12 with a LOD score of 6.1.

On Chromosome 12 a QTL influencing mean corpuscular volume was detected mapping between 35.0 and 68.8 Mb with a LOD score of 4.9 in the F2 analysis. This QTL was resolved into four individual QTL in the analysis of the combined F2 and F34 data:

Mcvq10 (mean corpuscular volume QTL 10) mapped between 59.8 and 61.1 Mb (23.2-25.6 cM) on Chr 12 with a LOD score of 5.5.

Mcvq11 (mean corpuscular volume QTL 11) mapped between 67.2 and 71.3 Mb (25.2-26.5 cM) on Chr 12 with a LOD score of 5.4.

Mcvq12 (mean corpuscular volume QTL 12) mapped between 72.9 and 76.8 Mb (28.1-32.3 cM) on Chr 12 with a LOD score of 5.9.

Mcvq13 (mean corpuscular volume QTL 13) mapped between 81.4 and 83.3 Mb (35.7-36.5 cM) on Chr 12 with a LOD score of 4.9.

Genes Fancm, Hif1a, Mthfd1 and Spnb1 are proposed candidate genes influencing the Mcvq QTL mapped to Chromosome 12. [Fig 5. C.]

References

• Original: J:182607 Bartnikas TB, et al., QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines. Mamm Genome. 2012 Jun;23(5-6):356-66
• All: 1 reference(s)