Abstract
The identification of genes that control susceptibility to testicular germ-cell tumours (TGCTs), the most common cancer affecting young men1, has been difficult. In laboratory mice, TGCTs arise from primordial germ cells2,3 in only the 129 inbred strains4, and susceptibility is under multigenic control. The spontaneously arising mutation Ter (ref. 5) on mouse chromosome 18 (Refs 6,7) increases TGCT frequency5,8 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 occurring strain variant allele that confers susceptibility to TGCTs and illustrates the power of CSSs in complex trait analysis.
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Acknowledgements
We thank K. Youngren and T. Nelson for expert technical assistance; P. Hunt for critical reading of the manuscript; R. Redline and M.-A. Handel for assistance with histology; and X. Montagutelli for helpful suggestions regarding the genetic analysis. This work was supported by NCI grant CA75056 and by a grant from the Howard Hughes Medical Institute to Case Western Reserve University School of Medicine.
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Matin, A., Collin, G., Asada, Y. et al. Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain. Nat Genet 23, 237–240 (1999). https://doi.org/10.1038/13874
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DOI: https://doi.org/10.1038/13874
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