title: A novel low-penetrance locus for familial glioma at 15q23-q26.3.
abstract: Epidemiological studies and case reports suggest that familial clustering of gliomas may occur in families that do not fit any known tumor syndromes. In the present study, 15 familial glioma pedigrees from a limited geographical area were hypothesized to carry the same low-penetrance susceptibility allele. We used a two-stage strategy for disease gene mapping. A genome scan in four glioma families revealed four interesting loci at chromosome arms 1q, 6q, 8p, and 15q. Additional markers in these regions provided evidence of significant linkage to 15q23-q26.3 with a maximum nonparametric linkage score of 3.35 with marker D15S130. Investigation of all 15 glioma families by association analysis (haplotype pattern mining) and through use of the transmission/disequilibrium test gave further evidence of significant association/transmission distortion at the same 15q locus (P = 0.02 and P = 0.03, respectively). No evidence of involvement of known tumor syndromes was obtained from the data provided by the linkage analysis or hospital records. Thus, the first genome-wide linkage analysis of familial glioma suggests a novel susceptibility locus at 15q23-q26.3.
authors.affiliation: Department of Pathology, Tampere University Hospital, FIN-33521 Tampere, Finland. niina.paunu@uta.fi
authors.forename: Niina
authors.initials: N
authors.lastname: Paunu
authors.forename: Päivi
authors.initials: P
authors.lastname: Lahermo
authors.forename: Päivi
authors.initials: P
authors.lastname: Onkamo
authors.forename: Vesa
authors.initials: V
authors.lastname: Ollikainen
authors.forename: Immo
authors.initials: I
authors.lastname: Rantala
authors.forename: Pauli
authors.initials: P
authors.lastname: Helén
authors.forename: Kalle O J
authors.initials: KO
authors.lastname: Simola
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human; D005910:Glioma / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D019683:Penetrance