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Camp NJ , Cannon-Albright LA , Farnham JM , Baffoe-Bonnie AB , George A , Powell I , Bailey-Wilson JE , Carpten JD , Giles GG , Hopper JL , Severi G , English DR , Foulkes WD , Maehle L , Moller P , Eeles R , Easton D , Badzioch MD , Whittemore AS , Oakley-Girvan I , Hsieh CL , Dimitrov L , Xu JF , Stanford JL , Johanneson B , Deutsch K , McIntosh L , Ostrander EA , Wiley KE , Isaacs SD , Walsh PC , Thibodeau SN , McDonnell SK , Hebbring S , Schaid DJ , Lange EM , Cooney KA , Tammela TLJ , Schleutker J , Paiss T , Maier C , Gronberg H , Wiklund F , Emanuelsson M , Isaacs WB
Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics
Human Molecular Genetics. 2007 Jun;16(11) :1271-1278
PMID: ISI:000248053300001   
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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.