The 5' end of the BRCA1 gene lies within a duplicated region of human chromosome 17q21.

To begin to address the hypothesis that abnormal regulation of the breast/ovarian cancer susceptibility gene BRCA1 is a critical step in sporadic breast/ovarian tumorigenesis, we have determined the detailed structure of the BRCA1 genomic region. We show that this region of the genome contains a tandem duplication of approximately 30 kilobases, which results in two copies of BRCA1 exons 1 and 2, of exons 1 and 3 of the adjacent 1A1-3B gene and of the previously reported 295 base pair intergenic region. Sequence analysis of the duplicated exons of BRCA1 and 1A1-3B and flanking genomic DNA reveals maintenance of the intron-exon structure and a high degree of nucleotide sequence identity, suggesting that these are non-processed pseudogenes and that the duplication is a recent event in evolutionary terms. We also show that a processed pseudogene of the acidic ribosomal phosphoprotein P1 (ARPP1) is inserted directly upstream of pseudo-BRCA1 exon 1A. We believe that these findings could not only confound BRCA1 mutation analysis, but could have implications for the normal and abnormal regulation of BRCA1 transcription, translation and function.