Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs)
Version of Record online: 7 APR 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 116, Issue 3, pages 487–491, 1 September 2005
How to Cite
Yang, X., Beerman, M., Bergen, A. W., Parry, D. M., Sheridan, E., Liebsch, N. J., Kelley, M. J., Chanock, S. and Goldstein, A. M. (2005), Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). Int. J. Cancer, 116: 487–491. doi: 10.1002/ijc.21006
- Issue online: 10 JUN 2005
- Version of Record online: 7 APR 2005
- Manuscript Accepted: 14 DEC 2004
- Manuscript Received: 5 OCT 2004
- Cancer Epidemiology and Biostatistics Fellowship Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute
- VA Merit Award
- single nucleotide polymorphism (SNP);
- genetic heterogeneity
Chordoma, a rare bone tumor originating from notochordal remnants, has a genetic predisposition in some families. Previously, we performed linkage analysis using microsatellite (STR) markers on 3 unrelated chordoma kindreds (16 patients with chordoma) and reported significant evidence for linkage to chromosome 7q33 (Zmax = 4.78) with a minimal disease gene region of 11 cM. In our present study, we performed linkage analysis in these 3 families using chromosome 7 single nucleotide polymorphisms (SNPs). Parametric and nonparametric multipoint analyses showed significant linkage to 7q markers with p < 0.001 and Zmax = 2.77, respectively. The minimal disease gene region was not reduced by combined SNP and STR haplotype analysis compared to the previous STR haplotype analysis alone. We genotyped members of a fourth chordoma family with SNP and STR markers for chromosome 7q and for 1p36, the location of a previously reported chordoma locus. Affected members of this family did not share a common haplotype on 7q, and the family did not show evidence of linkage to 1p36. Thus, we corroborated a chordoma locus on chromosome 7q in the 3 original families and demonstrated evidence for genetic heterogeneity in the fourth family. Our study also provided insights into some limitations and analytical complexities associated with using a dense SNP marker set in linkage analysis of complex pedigrees. © 2005 Wiley-Liss, Inc.