Mleu3^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Mleu3^C57BL/6J
• Name: myeloid leukemia survival 3; C57BL/6J
• MGI ID: MGI:3811141
• QTL: Mleu3 Location: unknown Genetic Position: Chr11, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

This QTL was identified in animals carrying the Tg(CTSG-PML/RARA)135Ley transgene.

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

J:139159

Linkage analysis was performed using 282 male (SWR/J x B6;C3H-Tg(CTSG-PML/RARA)135Ley)F2 animals to identify QTLs associated with susceptibility to ENU-induced acute myelogenous leukemia (AML). The Tg(CTSG-PML/RARA)135Ley) transgene confers sensitivity to spontaneous or induced myelogenous leukemia. F2 transgenic animals display earlier onset of AML, increased AML incidence and decreased survival time with or without ENU treatment compared to non-transgenic animals. Parental strain SWR/J is susceptible to ENU-induced AML whereas C57BL/6J and C3H/HeJ are resistant. Half of transgenic F2 animals were administered ENU at 9 to 10 weeks of age and the other half of transgenic F2 animals were left untreated. Genome scan utilized 384 SNP markers at a 4 cM resolution. Mice were sacrificed at 14 months of age or when they reached moribund state.

On mouse Chromosome 1, significant linkage to leukemia-free survival (Mleu1; myelogenous leukemia survival 1) and white blood cell count (Wbcc1; white blood cell count1) mapped to 42.837 cM (LPR=3.94) and 24 cM (LPR=3.3), respectively. Both QTLs were identified in ENU-treated animals. The closest associated marker for Mleu1 is rs13476036 and the 1-LPR confidence interval spans 39 cM to 46 cM. SWR/J-derived alleles at Mleu1 appear to confer increase survival in ENU-treated animals. Bcl2 is a potential candidate gene for Mleu1. The closest associated marker for Wbcc1 is rs6206420 and the 1-LPR confidence interval spans 17 cM - 31 cM. SWR/J-derived alleles at Wbcc1 conferdecreased white blood cell count in ENU-treated animals.

On mouse Chromosome 2, linkage to leukemia-free survival at the chromosome-wide level mapped to 47 cM near rs3669077 (LPR=2.53). This locus spans 37 cM to 55.3 cM and is named Mleu2 (myelogenous leukemia survival 2). SWR/J-derived alleles at Mleu2 confer decreased survival in non-ENU treated animals.

On mouse Chromosome 6, linkage to spleen weight mapped to 67 cM near rs13479087 (LPR=2.62). This locus is named Spw1 (spleen weight 1). The 1-LPR confidence interval spans 53 cM to the terminal end of chromosome 6. SWR/J-derived alleles confer increased spleen weight in ENU-treated animals with a recessive mode of inheritance. In untreated animals, SWR/J-derived alleles at Spw1 confer decreased spleen weight with a recessive mode of inheritance.

On mouse Chromosome 7, linkage to spleen weight mapped to 11 cM near rs6239372 (LPR=3.13). This locus spans 0 cM to 20 cM and is named Spw2 (spleen weight 2). SWR/J-derived allelesat Spw2 confer decreased spleen weight in ENU-treated and non-treated animals.

Significant linkage to leukemia-free survival at the chromosome-wide level mapped to mouse Chromosome 11 at 54 cM with LPR=2.48. This locus spans 50 cM to 57 cM and is named Mleu3 (myelogenous leukemia survival 3). The closest associated marker is rs13481161. Heterozygosity at Mleu3 confers increased survival in ENU-treated animals compared to homozygotes of either parental genotype. Spleen weight QTLs mapped to 1 cM (Spw3, spleen weight 3) near rs13480834 (LPR=4.24) in non-treated animals and 42 cM (Spw4, spleen weight 4) near rs6384101 (LPR=2.47) in ENU-treated animals. The 1-LPR confidence interval for Spw3 spans 0 cM to 6 cM; and for Spw4 the confidence interval spans37 cM -54 cM. SWR/J-derived alleles at Spw3 confer recessive increased spleen weight in non-treated animals. At Spw4, SWR/J-derived alleles confer recessive decreased spleen weight in ENU-treated animals. The overlapping QTL intervals of Mleu3 and Spw4 may suggest a common underlying genetic factor for these traits.

On mouse Chromosome 15, linkage to white blood cell count in ENU-treated animals mapped to 23.879 cM near rs13482609 (LPR=2.75). This locus spans 16 cM to 34 cM and is named Wbcc2 (white blood cell count 2). SWR/J-derived alleles at Wbcc2 confer increased white blood cell count in ENU-treated animals.

Linkage to spleen weight mapped to 16.5 cM on mouse Chromosome 16 near rs4167843 (LPR=2.48). This locus spans 7 cM to 31 cM and is named Spw5 (spleen weight 5). SWR/J-derived alleles at Spw5 confer dominantly decreased spleen weight in ENU-treated animals and increased spleen weight in non-treated animals.

On mouse Chromosome 19, chromosome-wide significant linkage to leukemia-free survival in ENU-treated animals mapped to24.989 cM near rs3655407 (LPR=2.99). This locus spans 14 cM to 46 cM and is named Mleu4 (myeloid leukemia survival 4). SWR/J-derived alleles at Mleu4 confer decreased survival. White blood cell count mapped to 47 cM near rs3718687 with chromosome-widesignificance of LPR=2.85. This locus spans 36 cM to the terminal end of chromosome 19 and is named Wbcc3 (white blood cell count 3). SWR/J-derived alleles at Wbcc3 confer increase white blood cell count in ENU-treated and non-treated animals. The overlapping QTL intervals of Mleu4 and Wbcc3 may suggest a common genetic factor for these traits.

Chromosome-wide significant linkage to leukemia-free survival in non-treated animals mapped to 59.634 cM on mouse Chromosome X near rs13484113 (LPR=2.26). This locus spans 49 cM to the terminal end of chromosome X and is named Mleu5 (myeloid leukemia survival 5). SWR/J-derived alleles at Mleu5 confer decreased survival in non-treated animals.

References

• Original: J:139159 Funk RK, et al., Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice. Blood. 2008 Aug 15;112(4):1434-42
• All: 1 reference(s)