Faculty Research 1990 - 1999
Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain.
Document Type
Article
Publication Date
1999
Keywords
Animal, Chromosomes, Crosses-Genetic, Data-Interpretation-Statistical, Female, Genetic-Predisposition-to-Disease, Genotype, Germinoma, Male, Mice, Mice-Inbred-Strains, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Testicular-Neoplasms
First Page
237
Last Page
240
JAX Source
Nat Genet 1999 Oct; 23(2):237-40.
Grant
CA75056/CA/NCI
Abstract
The identification of genes that control susceptibility to testicular germ-cell tumours (TGCTs), the most common cancer affecting young men, has been difficult. In laboratory mice, TGCTs arise from primordial germ cells in only the 129 inbred strains, and susceptibility is under multigenic control. The spontaneously arising mutation Ter (ref. 5) on mouse chromosome 18 (Refs 6,7) increases TGCT frequency on a 129/Sv background. We originally used Ter in genetic crosses to identify loci that control tumorigenesis. A genome scan of tumour-bearing progeny from backcrosses between the 129/Sv-Ter/+ and MOLF/Ei strains provided modest evidence that MOLF-derived alleles on chromosome 19 enhance development of bilateral TGCTs (ref. 9). To obtain independent evidence for linkage to the MOLF chromosome, we made an autosomal chromosome substitution strain (CSS; or 'consomic strain') in which chromosome 19 of 129/Sv+/+ was replaced by its MOLF-derived homologue. The unusually high frequency of TGCTs in this CSS (even in the absence of the Ter mutation) provides evidence confirming the genome survey results, identifies linkage for a naturally occuring strain variant allele that confers susceptibility to TGCTs and illustrates the power of CSSs in complex trait analysis.
Recommended Citation
Matin A,
Collin GB,
Asada Y,
Varnum D,
Nadeau JH.
Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain. Nat Genet 1999 Oct; 23(2):237-40.