Hgbq7^SM/J
QTL Variant Detail

Summary

• QTL variant: Hgbq7^SM/J
• Name: hemoglobin QTL 7; SM/J
• MGI ID: MGI:5812332
• QTL: Hgbq7 Location: unknown Genetic Position: Chr6, 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 (p^0.05 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:

QTL Mchq3 (mean corpuscular hemoglobin QTL 3) mapped to Chromosme 6 with a LOD score of 5.0 between 49.1 and 147.4 Mb (27.7-80.5 cM) in the F2 analysis. In the combined analysis of F2 and F34 data the map interval was refined between 54.2 and 73.4 Mb (30.3-35.9 cM) with a LOD score of 6.1. Genes Nt5c3 and Snca are proposed candidate genes for QTL Mchq3 [Fig1.A.]

QTL Hgbq7 (hemoglobin QTL 7) mapped to Chromosome 6 in the combined F2 and F34 analysis between 84.0 and 89.1 Mb (41.1-42.5 cM) with a LOD score of 4.9. Genes Exoc6b, Add2, Pcbp1 and Nfu1 are proposed cadidate genes for Hbbq7 [Fig 1.B.]

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)