Radpf1^C3H/Kam
QTL Variant Detail

Summary

• QTL variant: Radpf1^C3H/Kam
• Name: radiation pulmonary fibrosis 1; C3H/Kam
• MGI ID: MGI:2159708
• QTL: Radpf1 Location: Chr17:16835455-33819843 bp Genetic Position: Chr17, cM position of peak correlated region/allele: 18.59 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C3H/Kam

Variant description

• Allele Type: QTL
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Radpf1 exhibits additive inheritance.

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

J:44302

Markers on mouse Chromosomes 17 (D17Mit13) and 11 (D11Mit5, D11Mit320) linked to previously identified QTLs for bleomycin induced pulmonary fibrosis Bplpf1 and Bplpf2, respectively, were screened for linkage to radiation induced pulmonary fibrosis susceptibility in 250 (C57BL/6J x C3Hf/Kam)F2 animals. Parental strain C57BL/6J is susceptible to radiation induced pulmonary fibrosis whereas C3Hf/Kam is resistant. (C57BL/6J x C3Hf/Kam)F1 hybrids exhibit fibrosis susceptibility intermediate to the 2 parental strains. D17Mit13 showed significant linkage to radiation induced fibrosis susceptibility (P=3.0 x 10^-6) and this locus was designated Radpf1 (radiation pulmonary fibrosis 1). C57BL/6J-derived alleles confer an increase in mean fibrotic score at this locus. Radpf1 follows an additive mode of inheritance. Chromosome 11 markers did not exhibit linkage to radiation induced pulmonary fibrosis susceptibility.

J:81233

Genome scan was performed on 94 phenotypically extreme (C57BL/6J X C3Hf/Kam)F2 mice using 154 markers at an average resolution of 10 cM to detect QTLs associated with susceptibility to radiation-induced pulmonary fibrosis. Parental strain C57BL/6J is susceptible to radiation-induced pulmonary fibrosis while parental strain C3Hf/Kam is resistant. 4 QTLs identified in this study account for 70% of the genetic contribution towards this trait.

A previously identified QTL mapping near the H2 locus on mouse Chromsome 17, Radpf1, was detected in this study. Radpf1 gives peak linkage with LOD=4.2 at D17Mit198 with C57BL/6J-derived alleles conferring additively inherited increased incidence of radiation-induced pulmonary fibrosis. Markers D17Mit213 (9.33 cM) andD17Mit16 (17.4 cM) define the QTL interval of Radpf1. Additional studies with congenic strains confirmed the inheritance of Radpf1.

On distal mouse Chromosome 1, a locus giving peak linkage (LOD=4.5) at D1Mit206 (95.8 cM) was identified and named Radpf2.C57BL/6J-derived alleles confer increased incidence of radiation-induced pulmonary fibrosis with additive effects at this locus. The QTL interval of Radpf2 spans 73 cM to 101.2 cM flanked by markers D1Mit102 and D1Mit406, respectively.

Radpf3 mapped to 60.55 cM on mouse Chromosome 6 with a peak LOD score of 4.6 at D6Mit254. C3Hf/Kam-derived alleles confer increased incidence of radiation-induced pulmonary fibrosis with recessive inheritance in female animals. Markers D6Mit366 (50.5 cM) and D6Mit15 (74cM) define the QTL interval of Radpf3.

Radpf4 mapped to 32 cM on mouse Chromosome 18 with a peak LOD score of 3.9 at D18Mit52. C57BL/6J-derived alleles confer increased incidence of radiation-induced pulmonary fibrosis with additive effects at this locus. The QTL interval of Radpf4 spans 27 cM to 41 cM flanked by markers D18Mit53 and D18Mit207, respectively.

A locus on mouse Chromosome 19 reached suggestive significance with a LOD score of 2.9 between D19Mit13 (33 cM) and D19Mit18 (26 cM).

References

• Original: J:44302 Haston CK, et al., Murine susceptibility to radiation-induced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis. Cancer Res. 1997 Dec 1;57(23):5286-91
• All: 2 reference(s)