Founder effect at PGL1 in hereditary head and neck paraganglioma families from the Netherlands.
PGL1, a gene responsible for hereditary paragangliomas of the head and neck, recently was mapped to a 2-cM interval on chromosome 11q22-q23, by linkage and haplotype-sharing analysis of a large multibranch Dutch family. We determined the disease-linked haplotype, as defined by 13 markers encompassing a large interval on 11q21-q23, in 10 additional families ascertained from the same geographical locale. Alleles were identical for six contiguous markers, spanning a genetic distance of 6 cM and containing PGL1. Despite this strong indication of a common ancestor, no kinships between the families could be demonstrated through genealogical surveys going back to 1800 a.d. We conclude that a single ancestral mutation is responsible for most, if not all, hereditary paragangliomas, in this region of The Netherlands, and that strong founder effects may exist at the PGL1 locus.
van Schothorst
E M
EM
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Jansen
J C
JC
Grooters
E
E
Prins
D E
DE
Wiersinga
J J
JJ
van der Mey
A G
AG
van Ommen
G J
GJ
Devilee
P
P
Cornelisse
C J
CJ
D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000097:blood; D005190:Family; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes; D008297:Male; D009426:Netherlands; D009679:Nuclear Family; D010235:Paraganglioma / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction
D005819:Genetic Markers; D004247:DNA