Pldmq2^FVB/NJ
QTL Variant Detail

Summary

• QTL variant: Pldmq2^FVB/NJ
• Name: pleiotropic diet and mammary tumor QTL 2; FVB/NJ
• MGI ID: MGI:3795558
• QTL: Pldmq2 Location: unknown Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: FVB/NJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased average metastasis number and increased average metastasis density in females on a high-fat diet compared to M16i. (J:136011)

Notes

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

J:136011

Linkage analysis was performed on 615 (M16i x FVB/NJ-TgN(MMTV-PyVT)634Mul)F2 animals to identify QTLs associated with obesity, diet, and mammary tumor susceptibility and metastasis. At 4 weeks of age male and female F2 animals were randomly assigned to ahigh-fat (45% fat) diet or normal (10% fat) diet. Body weight was measured at 3, 6, 9 weeks of age and at sacrifice. Onset of mammary tumor development was phenotyped for F2 animals hemizygous for the transgene starting at 4 weeks of age via palpation three times a week. Pulmonary metastasis was also phenotyped. Animals on the high-fat diet displayed earlier mammary tumor onset and higher metastatic index compared to animals on the low-fat diet. Several novel mammary tumor metastasis loci were detected. Only one locus on chromosome 9 was also identified in a previous analysis using the same animals for diet and body composition interactions.

Significant linkage to mammary tumor onset (LOD=4.62), tumor metastasis in females (LOD=3.78), and tumor count inmales on high-fat diet (LOD=3.53) mapped to a broad region on mouse Chromosome 1. This locus is named Pldmq1 (pleiotropic diet and mammary tumor QTL 1). Linkage to tumor onset in males and the pooled population and metatstasis in females mapped to approximately 10 cM while tumor count and tumor onset in females mapped to 68 cM. The Pldmq1 locus spans 4 cM to 93 cM. For phenotypes pertaining to tumor onset in the pooled population and metastasis in females a difference was observed between high- and low-fat diets. Pldmq1 explains 10.4% of the tumor onset variance. FVB/NJ-derived alleles at Pldmq1 confer increased pulmonary tumor metastases and mammary tumor onset in females and increased mammary tumor count in males. This allele also confers decreased timeof tumor onset in males and the pooled population.

Linkage to inguinal tumor weight in females mapped to 39.5 cM on mouse Chromosome 5 with LOD=3.86. This locus is named Dmq1 (diet and mammary tumor QTL 1). The QTL confidence interval spans 24.5 cM to85.5 cM. FBV/NJ-derived alleles at Dmq1 confer increased inguinal tumor weight in females.

Linkage to mammary tumor onset in females mapped to 42 cM on mouse Chromosome 7 with LOD=3.82. The confidence interval spans 17 cM to 46 cM and the locus is namedDmq2 (diet and mammary tumor QTL 2). FVB/NJ-derived alleles confer decreased time to mammary tumor onset in females.

A pleiotropic locus exhibiting linkage to average metastasis number (LOD=3.29), average metastasis density (LOD=2.89) and number of metastases (LOD=3.74) infemales mapped to approximately 31 cM on mouse Chromosome 8. This locus also displays linkage to mammary tumor onset (LOD=31.7) in the pooled population and is named Pldmq2 (pleiotropic diet and mammary tumor QTL 2). The Pldmq2 QTL confidence interval spans 2 cM to 74 cM. M16i-derived alleles at Pldmq2 confer increased number of pulmonary metastases in females while FVB/NJ-derived alleles confer increased average metastasis number and density.

Plbcq6 (pleiotropic body composition QTL6) maps to 47 cM on mouse Chromosome 9 and was identified in a previous analysis for body composition using the same cross (MGI reference number J:132804). In the current analysis Plbcq6 displays significant linkage to mammary tumor onset in females on ahigh-fat diet (LOD=3), mammary tumor onset in the pooled population (LOD=4.86), axillary tumor weight in males (LOD=2.36) and tumor count in males on a high-fat diet (LOD=3.53). Peak linkage in this study occurs at 56 cM and the QTL interval spans 4 cM to 69 cM. Plbcq6 explains 10.9% of the tumor onset variance. M16i-derived alleles at Plbcq6 confer increased axillary tumor weight and tumor count in males. FVB/NJ-derived alleles at Plbcq6 confer increased tumor time of onset in females and the pooled population. Plbcq6 colocalizes with mammary tumor QTL Apmt2 (55 cM).

Linkage to number of pulmonary metastases in females mapped to 14 cM on mouse Chromosome 11 (LOD=3.17). This locus is named Dmq3 (diet and mammary tumor QTL 3). The phenotypic effects of Dmq3 show differences between the high- and low-fat diets. The Dmq3 QTL interval spans 5 cM to 73 cM. M16i-derived alleles at Dmq3 confer increased number of pulmonary metastases in females.

An interval on mouse Chromosome 13 between 3 cM and 61 cM exhibits linkage to average metastatic density (LOD=3.09), average metastatic number (LOD=3.49) and mammary tumor onset (LOD=2.94) in females. Peak linkage occurs at approximately 13 cM and this locus is named Pldmq3 (pleiotropic diet and mammary tumor QTL 3).The phenotypes for average metastatic density and number are observed in only the high-fat diet group. FVB/NJ-derived alleles at Pldmq3 confer increased average metastatic number and density in females and decreased tumor time of onset in females.

Pldmq4 (pleiotropic diet and mammary tumor QTL 4) maps to an interval on mouse Chromosome 14 between 7 cM and 57 cM. This locus is associated with axillary tumor weight in males on the low-fat diet (LOD=3.2), onset of mammary tumors in females on the low-fat diet (LOD=3.07) and tumor count (LOD=LOD=2.8) in females. A difference was observed for mammary tumor count phenotype in females between the high- and low-fat diets. Peak linkage occurs around 40 cM. FVB/NJ-derived alleles at Pldmq4 confer increased axillary tumor weight in males and tumor time of onset infemales. This allele also confers decreased mammary tumor count in females.

Linkage to axillary tumor weight in females (LOD=2.63) and mammary tumor onset in males on a low-fat diet (LOD=2.87) mapped to approximately 42 cM on mouse Chromosome 17. This locus is named Pldmq5 (pleiotropic diet and mammary tumor QTL 5). The Pldmq5 confidence interval spans 8 cM to 54 cM. FVB/NJ-derived alleles at Pldmq5 confer increased axillary tumor weight in females and decreased tumor time of onset in males.

Dmq4 (dietand mammary tumor QTL 4) maps to 15.5 cM on mouse Chromosome 19 and shows linkage to number of pulmonary metastases in females on a high-fat diet (LOD=4.21). The confidence interval for this locus spans 7.5 cM to40.5 cM. FVB/NJ-derived alleles at Dmq4 confer increased pulmonary metastases in females. Previously identified metastasis suppressor QTL Mtes1 (4 cM) colocalizes with Dmq4.

References

• Original: J:136011 Gordon RR, et al., Genotype X diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis. Mamm Genome. 2008 Mar;19(3):179-89
• All: 1 reference(s)