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

Xiaohong Yang, Michael Beerman, Andrew W. Bergen, Dilys M. Parry, Eamonn Sheridan, Norbert J. Liebsch, Michael J. Kelley, Stephen Chanock, Alisa M. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalInternational Journal of Cancer
Volume116
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • Chordoma
  • Genetic heterogeneity
  • Linkage
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs)'. Together they form a unique fingerprint.

Cite this