Mchcq1^SM/J
QTL Variant Detail

Summary

• QTL variant: Mchcq1^SM/J
• Name: mean corpuscular hemoglobin concentration QTL 1; SM/J
• MGI ID: MGI:5812341
• QTL: Mchcq1 Location: unknown Genetic Position: Chr7, 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 7 a QTL influencing mean corpuscular volume was detected mapping between 42.2 and 115.2 Mb with a LOD score of 5.1 in the F2 analysis. This QTL was resolved into three individual QTL in the analysis of the combined F2 and F34 data:

Mcvq7 (mean corpuscular volume QTL 7) mapped between 44.9 and 68.3 Mb (27.9-33.8 cM) on Chr7 with a LOD score of 7.6.

Mcvq8 (mean corpuscular volume QTL 8) mapped between 92.1 and 98.4 Mb (45.6-47.1 cM) on Chr 7 with a LOD score of 6.3.

Mcvq9 (mean corpuscular volume QTL 9) mapped between 99.2 and 110.7 Mb (48.1-51.7 cM) on Chr 7 with a LOD score of 5.8.

Genes Picalm and Klf13 are proposed candidate genes for the Mcvq QTL mapping to Chromosome 7. [Fig 2.C.].

On Chromosome 7 a hemoglobin QTL was detected mapping between 13.5 and 123.7 Mb with a LOD score of 7.1 in the F2 analysis. This QTL was resolved into five individual QTL in the analysis of the combined F2 and F34 data:

Hgbq8 (hemoglobin QTL 8) mapped between 30.1 and 30.2 Mb (11.4-14.6 cM) on Chr 7 with a LOD score of 5.3.

Hgbq9 (hemoglobin QTL 9) mapped between 37.4 and 40.2 Mb (20.7-22.2 cM) on Chr 7 with a LOD score of 5.5.

Hgbq10 (hemoglobin QTL 10) mapped between 42.3 and 56.4 Mb (23.8-30.4 cM) on Chr 7 with a LOD score of 6.9.

Hgbq11 (hemoglobin QTL 11) mapped between 78.5 and 78.8 Mb (40.5-40.7 cM) on Chr 7 with a LOD score of 4.6.

Hgbq12 (hemoglobin QTL 12) mapped between 99.2 and 107.4 Mb (48.1-50.5 cM) on Chr 7 with a LOD score of 7.2.

Genes Picalm, Hamp1, Hamp2, Gpi1 and Cebpa are proposed genes for the Chromosome 7 QTL influencing hemoglobin levels. [Fig 2.A.]

QTL Mchcq1 (mean corpuscular hemoglobin concentration QTL 1) was detected on Chromosome 7 in the F2 analysis mapping between 35.8 and 123.7 Mb with a LOD score of 7.3. In the combined data analysis the location was refined between 92.7 and 110.7 MB (46.8-51.7 cM) with a LOD score of 12.4.

Genes Picalm, Hbb-b1, Hbb-b2,Hbb-bh1, Hbb-y and Hbb-ar are proposed candidate genes influencing the Mchcq1 QTL. [Fig 2.B.]

QTL Rbc7 (red blood cell count 7) mapped to Chromosome 7 between 27.4 and 101.6 Mb in the F2 analysis with a LOD score of 5.5. In the combined data analysis with F2 and F34 data the interval was refined between 44.9 and 69.9 Mb (25.4-35.4 cM) with a LOD score of 69.9.

Gene Klf13 is a proposed candidate gene mapping within the Rbc7 QTL. [Fig 2.D.]

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)