title: Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb.
abstract: Genetic studies suggest that hereditary prostate cancer is a genetically heterogeneous disease with multiple contributing loci. Studies of high-risk prostate cancer families selected for aggressive disease, analysis of large multigenerational families, and a meta-analysis from the International Consortium for Prostate Cancer Genetics (ICPCG), all highlight chromosome 22q12.3 as a susceptibility locus with strong statistical significance. Recently, two publications have narrowed the 22q12.3 locus to a 2.18 Mb interval using 54 high-risk families from the ICPCG collaboration, as defined by three recombination events on either side of the locus. In this paper, we present the results from fine mapping studies at 22q12.3 using both haplotype and recombination data from 42 high-risk families contributed from the Mayo Clinic and the Prostate Cancer Genetic Research Study (PROGRESS) mapping studies. No clear consensus interval is present when all families are used. However, in the subset of 14 families with >/=5 affected men per family, a 2.53-Mb shared consensus segment that overlaps with the previously published interval is identified. Combining these results with data from the earlier ICPCG study reduces the three-recombination interval at 22q12.3 to approximately 1.36 Mb.
authors: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Bo
authors: B
authors: Johanneson
authors: Shannon K
authors: SK
authors: McDonnell
authors: Danielle M
authors: DM
authors: Karyadi
authors: Scott J
authors: SJ
authors: Hebbring
authors: Liang
authors: L
authors: Wang
authors: Kerry
authors: K
authors: Deutsch
authors: Laura
authors: L
authors: McIntosh
authors: Erika M
authors: EM
authors: Kwon
authors: Miia
authors: M
authors: Suuriniemi
authors: Janet L
authors: JL
authors: Stanford
authors: Daniel J
authors: DJ
authors: Schaid
authors: Elaine A
authors: EA
authors: Ostrander
authors: Stephen N
authors: SN
authors: Thibodeau
mesh_terms: D002892:Chromosomes, Human, Pair 22; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics*