Raml1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Raml1^C57BL/6J
• Name: radiation induced acute myeloid leukemia 1; C57BL/6J
• MGI ID: MGI:3655652
• QTL: Raml1 Location: unknown Genetic Position: Chr18, cM position of peak correlated region/allele: 6.36 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers sensitivity to radiation-induced chromosome 2 deletions compared to CBA/Ca. (J:105074)

Notes

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

J:105074

Susceptibility to radiation induced acute myeloid leukemia (AML) was mapped by genomic microsatellite analysis of 9 inbred strains. AML susceptible strains, such as CBA/H and CBA/Ca, exhibit a high frequency of chromosome 2 deletions in bone marrow cellsfollowing whole body irradiation whereas resistant strains, such as C57BL/6J, do not. Loci were detected on mouse Chromosomes 3, 4, 8, and 18. A limited (CBA/Ca x C57BL/6J)F1 x C57BL/6J backcross was used to confirm the QTLs.

Raml1 (radiation induced acute myeloid leukemia 1) mapped to mouse Chromosome 18 with strongest linkage at D18Mit146 (4 cM) and D18Mit229 (4 cM). C57BL/6J-derived alleles at Raml1 confer sensitivity to radiation induced chromosome 2 deletions and, by association, AML. Loss of heterozygosity was not observed in this region. Potential candidate genes in this region are Rbbp8, Riok3 (3 cM), 3110002H16Rik (Mic1), Npc1 (4 cM), Ankrd29, and Lama3 (3 cM). Rbbp8 was identified as a strong candidate as this gene is upregulated in response toX-irradiation inCBA mice. Raml1 is syntenic to human 18q11, a region implicated in 322 cases of cancer.

Raml2 (radiation induced acute myeloid leukemia 2) mapped to 61.8 cM on mouse Chromosome 3 near D3Mit319. This locus is syntenic to human Chromosome 4q25. Bomb1 (61.8cM) is a previously identified bone marrow lymphoma QTL co-localizing with Raml2.

Raml3 (radiation induced acute myeloid leukemia 3) mapped to 55.2 cM on mouse Chromosome 4 near D4Mit248. This locus is syntenic to human Chromosome 1p34. Mycl1 (previously Lmyc; 55 cM) is a potential candidate gene for Raml3. Previously identified tumor susceptibility QTLs Thyls (55 cM) and Skts7 (56 cM) are found near Raml3.

Raml4 (radiation induced acute myeloid leukemia 4) mapped to 33 cM on mouse Chromosome 8 near D8Mit178. This locus is syntenic to human Chromosome 19p13. Rab3a (32.6 cM) and Rab8a (33 cM) are potential candidate genes mapping near Raml4.

Raml5 (radiation induced acute myeloid leukemia 5) mapped to mouse Chromosome 13 near D13Mit23. Nsd1, Mxd3 (formerly Mad3; 32 cM), and Msx2 (formerly Hox8; 32 cM) are potential candidate genes for Raml5.

References

• Original: J:105074 Darakhshan F, et al., Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay. Carcinogenesis. 2006 Feb;27(2):311-8
• All: 1 reference(s)