Hsm1^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Hsm1^C3H/HeJ
• Name: hereditary spherocytosis modifer 1; C3H/HeJ
• MGI ID: MGI:3041831
• QTL: Hsm1 Location: unknown Genetic Position: Chr12, cM position of peak correlated region/allele: 35.7 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Notes

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

J:89043

Linkage analysis was performed on a population of (C3H/HeJ-Slc4a1^wan/J x CAST/EiJ)F2 intercross animals to identify QTLs modifying hereditary spherocytosis (HS), a condition that results in spherical red blood cells and severe hemolytic anemia. Parental strain C3H/HeJ-Slc4a1^wan/J carries a mutation in Slc4a1 (C-to-T transition at nucleotide 3998) and exhibits the HS phenotype. Homozygous mutant animals display reduced red blood cell (RBC), hemoglobin, and hematocrit counts, reduced mean corpuscular volume (MCV), reduced mean corpuscular hemoglobin content (MCHC), and die 72 hours after birth. 96 polymorphic loci were genotyped.

Linkage to the MCV trait mapped to 32 cM on mouse Chromosome 12 near D12Mit156 (LOD=3.7) and is named Hsm1 (hereditary spherocytosis modifier 1). The 95% confidence interval of Hsm1 spans 28 cM - 40 cM. CAST/EiJ-derived alleles confer decreased MCV with dominant inheritance. This locus accounts for 9% of the phenotypic variance. Spnb1 maps near Hsm1 and is a candidate gene. Sequence analysis of Spnb1 revealed 3 amino acid differences between CAST/EiJ and C3H/HeJ but these changes do not suggest altered gene function. Western blot analysis did not reveal protein expression differences between CAST/EiJ and C3H/HeJ but Spnb1. Authors still consider Spnb1 a viable candidate gene.

A second QTL for the MCV trait mapped to a broad region of mouse Chromosome 6 from 40 cM - 80 cM. The peak LOD score occurred around D6Mit15 (74 cM). Authors speculate several linked QTLs exist within this region and further mapping will resolve these loci. This region accounts for 7% of the phenotypic variance.

Suggestive QTLs for the MCHC trait mapped to mouse Chromosomes 7 and 19.

References

• Original: J:89043 Peters LL, et al., Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency. Blood. 2004 Apr 15;103(8):3233-40
• All: 1 reference(s)