THE BRCA1 AND 1A1.3B PROMOTERS ARE PARALLEL ELEMENTS OF A GENOMIC DUPLICATION AT 17Q21

The results of experiments aimed at detecting polymorphisms and mutati ons in the BRCA1 promoter region as well as comparisons of two publish ed DNA sequences indicated that two similar but distinct copies of thi s region exist in the human genome, PCR primers specific for amplifica tion of each of the related sequences were developed and new genomic c lones corresponding to each of the two promoter regions were isolated from rearrangement-resistant libraries. Sequence analysis of the clone s and specific PCR products reveals two similar genomic arrangements o f head-to-head genes, The BRCA1 gene is closely apposed to a gene stru cture that is similar but not identical to 1A1.3B, and the 1A1.3B gene is apposed to a gene structure that has strong similarity to BRCA1 bu t also significant differences, STS analysis of YAC and P1 clones loca ted in the vicinity of BRCA1 indicates that these similar promoter reg ions are elements of a direct duplication, New hypotheses for genetic mechanisms that may be involved in breast and ovarian cancer etiology are raised by the identification of this duplicated genetic structure on chromosome 17q. (C) 1996 Academic Press, Inc.