Isolation of tetranucleotide repeat polymorphisms flanking the BRCA1 gene.

ABSTRACT

Large pools of cosmids from the BRCA1 region of human chromosome 17 were screened for tetranucleotide repeat polymorphisms by hybridizing shotgun subcloned pools with a mixture of 25 oligonucleotides. Identified subclones were PCR amplified and directly sequenced to design PCR primers for short tandem repeat polymorphism (STRP) analysis of family DNAs. With the identification of the BRCA1 gene and the observation that most mutations in this > 100-kb gene are unique, haplotyping and linkage analysis may play a significant role in diagnosis and carrier detection of BRCA1-associated breast and ovarian cancers. We report the characterization of 15 new STRPs flanking the BRCA1 locus.