Premium
Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs)
Author(s) -
Yang Xiaohong Rose,
Beerman Michael,
Bergen Andrew W.,
Parry Dilys M.,
Sheridan Eamonn,
Liebsch Norbert J.,
Kelley Michael J.,
Chanock Stephen,
Goldstein Alisa M.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21006
Subject(s) - genetics , biology , single nucleotide polymorphism , haplotype , genetic linkage , locus (genetics) , microsatellite , tag snp , snp , genetic marker , genotype , gene , allele
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. © 2005 Wiley‐Liss, Inc.