Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease
Liesel M FitzGerald, Briony Patterson, Russell Thomson, Andrea Polanowski, Stephen Quinn, Jesper Brohede, Timothy Thornton, David Challis, David A Mackey, Terence Dwyer, Simon Foote, Garry N Hannan, James Stankovich, James D McKay, Joanne L Dickinson
EUROPEAN JOURNAL OF HUMAN GENETICS | NATURE PUBLISHING GROUP | Published : 2009
Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13-q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (P=0.0017). Re-sequencing of eight prioritised candidate genes in the region in s..View full abstract
We thank Annette Banks, Kris Hazelwood, Sally Inglis and Annette Edwards for their assistance in creating genealogical records and/or sample collection; and Melanie Bahlo, Terence Speed and David Goldgar for useful suggestions and discussions about methods of linkage analysis. The Royal Hobart Hospital Research Foundation, The Cancer Council of Tasmania, CaPCure, The Mazda Foundation and Perpetual Charitable Trusts and the Australian Cancer Research Fund supported this study. Dr Dickinson is a Cancer Council of Tasmania Research Fellow. We are also greatly indebted to the participants of the TasPac study, the TCR staff, the Tasmanian Urologists and Pathologists, and the wider Tasmanian clinical and research community.