Ramls2^CBA/H
QTL Variant Detail

Summary

• QTL variant: Ramls2^CBA/H
• Name: radiation-induced acute myeloid leukemia sensitivity 2; CBA/H
• MGI ID: MGI:3722400
• QTL: Ramls2 Location: unknown Genetic Position: Chr6, cM position of peak correlated region/allele: 27.38 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: CBA/H

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: Heterozygosity for CBA/H and C57BL/6 alleles confer increased sensitivity to radiation-induced acute myeloid leukemia compared to homozygosity for CBA/H alleles. (J:82643)

Notes

Ramls2 is a low-penetrance QTL that increases relative risk for radiation-induced acute myeloid leukemia by approximately 2-fold.

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

J:82643

The inbred strain CBA/H displays increased susceptibility to radiation-induced acute myeloid leukemia (lifetime incidence of 20%) compared to inbred strain C57BL/6 (lifetime incidence of 7%). Linkage analysis was performed on a population of (CBA/H x C57BL/6)F1 x CBA/H animals to identify QTLs associated with susceptibility to radiation-induced acute myeloid leukemia (r-AML). A total of 1087 backcross animals were exposed to 3 Gy x-rays resulting in 67 animals affected with r-AML. A panel of 138 polymorphic markers spaced approximately 22 cM apart was genotyped in the 67 affected backcross animals. Two low-penetrance QTLs named Ramls1 (radiation-induced acute myeloid leukemia sensitivity 1) and Ramls2 (radiation-induced acute myeloid leukemia sensitivity2) were identified. It is thought Ramls1 and Ramls2 are involved in separate leukemogenic processes.

A minor locus for r-AML sensitivity mapped to 100 cM on mouse Chromosome 1 near D1Mit150. This locus is named Ramls1 (radiation-induced acute myeloid leukemia sensitivity 1). Excess homozygosity for CBA/H-derived alleles at Ramls1 is associated with increased relative risk (RR) for r-AML. A previously identified stem cell frequency QTL named Scfr1 (98 cM) maps near this locus.

A minor locus for r-AML sensitivity mapped to 27 cM on mouse Chromosome 6 near D6Mit384. This locus is associated with r-AML resistance and is named Ramls2 (radiation-induced acute myeloid leukemia sensitivity 2). Excess heterozygosity for CBA/H and C57BL/6 alleles at Ramls2 is associated with increased r-AML RR. Ramls2 is also associated with a high frequency of chromosome aberrations (maker chromosomes, trisomy, monosomy) in r-AML animals.

Suggestive linkages to r-AML sensitivity mapped to 7 cM on mouse Chromosome 4 near D4Mit292 (P=0.021) and 34 cM on mouse Chromosome 13 near D13Mit248 (P=0.043).

References

• Original: J:82643 Boulton E, et al., Low-penetrance genetic susceptibility and resistance loci implicated in the relative risk for radiation-induced acute myeloid leukemia in mice. Blood. 2003 Mar 15;101(6):2349-54
• All: 1 reference(s)