METHODS FOR THE DETECTION OF BREAKPOINTS IN REARRANGED GENOMIC SEQUENCES

摘要

Methods for detecting the amplifications of sequences in the BRCA1 locus, which sequences have ends consisting of or are framed with sequence stretches present at least twice in the BRCA1 locus, and which amplification results in at least two or at least three, especially three, tandem copies of the amplified sequence; methods for determining a predisposition to diseases or disorders associated with these amplifications, including predisposition to ovarian cancer or breast cancer and methods for detecting amplifications with similar features in other loci and/or for predicting breakpoints of such amplifications.

主权项

1. A method for in vitro prediction of a breakpoint associated with rearrangement in a nucleic acid of a biological sample comprising a nucleic acid representative of a chromosomal nucleic acid, comprising:
mapping the nucleic acid of the biological sample; determining a size and/or a confidence interval for the size of the rearrangement, a location and/or a confidence interval for the location of one breakpoint at one end of the rearrangement, and a location and/or a confidence interval for the location of the breakpoint at the other end of the rearrangement; determining sequence homology between predicted sequences of the locations determined for the breakpoints, such predicted sequences being taken from reference databases, by determining presence of one or more homologous sequence stretches with nucleotide identity of 80 to 98% of the nucleotides over the length of the sequence stretch, when each sequence stretch for which homology is determined in the nucleic acid has a length of at least 200 bp; within the identified homologous sequence stretches, determining strict sequence identity over a portion of the homologous nucleic acid sequences, wherein the strict identity exists over a sequence portion of about 25 bp to about 80 bp; and when such portions exist exhibiting such sequence identity, reporting that such portions are likely to comprise the breakpoint for sequence rearrangement.