title: Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics.
abstract: Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants) contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in 54 pedigrees selected to be informative for recombinant mapping from nine member groups of the International Consortium for Prostate Cancer Genetics (ICPCG). These 54 pedigrees included the 14 extended pedigrees from Utah and 40 pedigrees from eight other ICPCG member groups. The additional 40 pedigrees were selected from a total pool of 1213 such that each pedigree was required to contain both at least four prostate cancer (PRCA) cases and exhibit evidence for linkage to the chromosome 22q region. The recombinant events in these 40 independent pedigrees confirmed the previously proposed region. Further, when all 54 pedigrees were considered, the three-recombinant consensus region was narrowed down by more than a megabase to 2.2 Mb at chromosome 22q12.3 flanked by D22S281 and D22S683. This narrower region eliminated 20 annotated genes from that previously proposed, leaving only 11 genes. This region at 22q12.3 is the most consistently identified and smallest linkage region for PRCA. This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases.
authors.affiliation: University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, 391 Chipeta Way, Suite D, Salt Lake City, UT 84108, USA. nicola.camp@utah.edu
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.forename: James M
authors.initials: JM
authors.lastname: Farnham
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Baffoe-Bonnie
authors.forename: Asha
authors.initials: A
authors.lastname: George
authors.forename: Isaac
authors.initials: I
authors.lastname: Powell
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Lovise
authors.initials: L
authors.lastname: Maehle
authors.forename: Pal
authors.initials: P
authors.lastname: Moller
authors.forename: Ros
authors.initials: R
authors.lastname: Eeles
authors.forename: Douglas
authors.initials: D
authors.lastname: Easton
authors.forename: Michael D
authors.initials: MD
authors.lastname: Badzioch
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Ingrid
authors.initials: I
authors.lastname: Oakley-Girvan
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Latchezar
authors.initials: L
authors.lastname: Dimitrov
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Bo
authors.initials: B
authors.lastname: Johanneson
authors.forename: Kerry
authors.initials: K
authors.lastname: Deutsch
authors.forename: Laura
authors.initials: L
authors.lastname: McIntosh
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: Scott
authors.initials: S
authors.lastname: Hebbring
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.forename: Thomas
authors.initials: T
authors.lastname: Paiss
authors.forename: Christiane
authors.initials: C
authors.lastname: Maier
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelsson
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
mesh_terms: D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007391:International Cooperation; D008126:Lod Score; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D012955:Societies, Medical