Identification of rare intronic variants defining novel BRCA haplotypes

Sanger DNA sequencing is widely used nowadays to identify germ-line alterations of cancer predisposition genes. Molecular diagnosis of hereditary risk of breast and ovarian cancer (HBOC) is mainly targeting BRCA1 and BRCA2, as carriers of deleterious mutations in any of these genes are at significantly higher risk of developing cancer than general population. Usual diagnosis performs a pre-screening step, followed by systematic sequencing of exons and exon/intron boundaries. Unfortunately, not all sequence variations found by sequencing are pathogenic. About one half of identified variants are of unclear clinical significance. Common single nucleotide polymorphisms (SNPs) are also usually detected, either heterozygous or homozygous. When systematically detected, SNPs can be used to define haplotypes, which are particularly useful in population disease studies or ethnogenomics. Frequent BRCA1 SNPs are well known, as well as associated haplotypes. Here we present some rare intronic variants defining novel BRCA1 haplotypes.