Nature Genetics
23, 237 - 240 (1999)
doi:10.1038/13874
Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strainAngabin Matin1, Gayle B. Collin2, Yoshinobu Asada3, Don Varnum2
& Joseph H. Nadeau11
Department of Genetics, Case Western Reserve University School of Medicine, and Center for Human Genetics & Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio 44106-4955, USA. 2
The Jackson Laboratory, Bar Harbor, Maine 04609, USA. 3
Department of Pedodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
Correspondence should be addressed to Joseph H. Nadeau jhn4@po.cwru.eduThe 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.
|
