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© 1993 Oxford University Press

RESEARCH-ARTICLE

Genetic mapping of the breast-ovarian cancer syndrome to a small interval on chromosome 17q12–21: exclusion of candidate genes EDH17B2 and RARA

Jacques Simard, Jean Feunteun1, Gilbert Lenoir2, Patricia Tonin3, Thlerry Normand, Van Luu The, Anne Vivler3, Dana Lasko3, Kenneth Morgan3,4, Guy A. Rouleau3,5, Henry Lynch6, Femand Labrie and Steven A. Narod3,*

Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University Quebec G1V 4G2, Canada 1Institut Gustave Roussy, Villejurf 2International Agency for Research on Cancer 150 Cours Albert Thomas, Lyon, France 3Department of Medicine, Division of Medical Genetics, Montreal General Hospital, McGil University 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada 4Department of Epidemiology and Biostatistics, and Centre for Human Genetics, McGill University Montreal, Canada 5Centre for Research in Neurosciences, McGill University Montreal, Canada 6Creighton Universrty School of Medicine, Department of Preventive Medicine and Public Health Omaha, NE, USA

* To whom correspondence should be addressed

Received April 7, 1993; Revised June 2, 1993; Accepted June 2, 1993

A susceptibility gene for hereditary breast-ovarian cancer, BRCA1, has been assigned by linkage analysis to chromosome 17q21. Candidate genes in this region Include EDH17B2, which encodes estradiol 17ß-hydroxysterold dehydrogenase II (17ß-HSD II), and RARA, the gene for retinolc acid receptor {alpha}. We have typed 22 breast and breast-ovarian cancer families with eight polymorphisms from the chromosome 17q12–21 region, including two in the EDH17B2 gene. Genetic recombination with the breast cancer trait excludes RARA from further consideration as a candidate gene for BRCA1. Both BRCA1 and EDH17B2 map to a 6 cM Interval (between THRA1 and D17S579) and no recombination was observed between the two genes. However, direct sequencing of overlapping PCR products containing the entire EDH17B2 gene In four unrelated affected women did not uncover any sequence variation, other than previously described polymorphisms. Mutations in the EDH17B2 gene, therefore do not appear to be responsible for the hereditary breast-ovarian cancer syndrome. Single meiotic crossovers In affected women suggest that BRCA1 is flanked by the loci RARA and D17S78.


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