Mchq16^SM/J
QTL Variant Detail

Summary

• QTL variant: Mchq16^SM/J
• Name: mean corpuscular hemoglobin QTL 16; SM/J
• MGI ID: MGI:5812205
• QTL: Mchq16 Location: unknown Genetic Position: Chr17, 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 17 a QTL influencing mean corpuscular hemoglobin was detected mapping between 0.0 and 63.2 Mb with a LOD score of 6.7 in the F2 analysis. This QTL was resolved into two individual QTL in the analysis of the combined F2 and F34 data:

Mchq15 (mean corpuscular hemoglobin QTL 15) mapped between 23.2 and 25.4 Mb (9.7-11.1 cM) on Chr 17 with a LOD score of 5.1.

Mchq16 (mean corpuscular hemoglobin QTL 16) mapped between 27.2 and 42.5 Mb (12.8-19.7 cM) on Chr 17 with a LOD score of 8.1.

Genes Narfl, Rps10, Srpk1, Cd320, Trim10, Pigq, Fance, March2, Neu1, and Vegfa are proposed candidate genes for Mchq QTL mapping to Chromosome 17. [Fig 6.A.]

On Chromosome 17, Hgbq13 (hemoglobin QTL 13) was detected mapping between 17.5 and 63.2 Mb with a LOD score of 6.7 in the F2 analysis. This QTL was resolved into an interval mapping between 23.5 and 25.4 Mb (10.4-10.8 cM) with a LOD score of 4.5 in the analysis of the combined F2 and F34 data.

Hgbq14 (hemoglobin QTL 14) was also detected on Chromosome 17. In the F2 analysis this QTL mapped between 75.1 and 85.5 Mb with a LOD score of 3.3. In the combined data analysis the Hgbq14 interval was refined between 31.4 and 48.1 Mb (15.9-22.5 cM) with a LOD score of 6.2.

References

• Original: J:186207 Duncan JS, et al., Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell. 2012 Apr 13;149(2):307-21
• All: 1 reference(s)