Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs).

Journal Article (Journal Article)

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 (Z(max) = 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 Z(max) = 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.

Full Text

Duke Authors

Cited Authors

  • Yang, X'R'; Beerman, M; Bergen, AW; Parry, DM; Sheridan, E; Liebsch, NJ; Kelley, MJ; Chanock, S; Goldstein, AM

Published Date

  • September 1, 2005

Published In

Volume / Issue

  • 116 / 3

Start / End Page

  • 487 - 491

PubMed ID

  • 15818627

International Standard Serial Number (ISSN)

  • 0020-7136

Digital Object Identifier (DOI)

  • 10.1002/ijc.21006


  • eng

Conference Location

  • United States