Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb

• Published in: Human genetics 2008-02, Vol.123 (1), p.65-75
• Main Authors: Johanneson, Bo, McDonnell, Shannon K., Karyadi, Danielle M., Hebbring, Scott J., Wang, Liang, Deutsch, Kerry, McIntosh, Laura, Kwon, Erika M., Suuriniemi, Miia, Stanford, Janet L., Schaid, Daniel J., Ostrander, Elaine A., Thibodeau, Stephen N.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Chromosomes; Chromosomes, Human, Pair 22; Classical genetics, quantitative genetics, hybrids; Consortia; Disease susceptibility; Fundamental and applied biological sciences. Psychology; Gene Function; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Haplotypes; Health aspects; Health sciences; Human; Human Genetics; Humans; Lod Score; Male; Medical research; Medical sciences; Metabolic Diseases; Methods, theories and miscellaneous; Molecular Medicine; Nephrology. Urinary tract diseases; Oncology, Experimental; Original Investigation; Pedigree; Prostate cancer; Prostatic Neoplasms - genetics; Public health; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-007-0451-y

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.