Hybridization assays for gene dosage analysis

摘要

Methods and compositions are provided for determining the dosage of target nucleic acid sequences. Probes comprising a crosslinking agent are combined with a sample that may comprise a target sequence that is complementary to a probe. Hybridization is allowed to occur between complementary sequences. The crosslinking agent is activated. Covalent bonds are formed between a probe and a target sequence if they are hybridized to each other, and a high-stringency wash step is employed to significantly lower background contamination. The crosslinked nucleic acids can then be detected and the resulting signal compared against a known diploid locus to determine the dosage of the target sequence. Dosage detection may be combined with the detection of polymorphisms, such as single nucleotide polymorphisms, to provide a more complete genetic profile at a locus or loci of interest.