Combined CGH and allele specific hybridisation method

摘要

The invention combines the fields of comparative genomic hybridization (CGH) analysis and SNP array analysis. It relates to methods for detecting and mapping genetic abnormalities associated with various diseases. In particular the invention provides a method for simultaneously performing array CGH and SNP array analysis on a genomic DNA sample comprising contacting a nucleic acid array which comprises a first probe set and a second probe set with a genomic DNA sample, comprising a test and reference sample, under hybridization conditions, comparing the amount of test sample and reference sample hybridized to the hybridization probes of the first probe set, comparing the amount of test sample and reference sample hybridized to the hybridization probes of the second probe set; and using the data obtained to determine the copy number of at least one locus; and at least one SNP in the genomic DNA sample.

主权项

1. A method for simultaneously performing array CGH and one or more of
SNP array analysis INDEL array analysis VNTR array analysis transposon array analysis on a genomic DNA sample, comprising steps (a) to (d): (a) contacting a nucleic acid array which comprises a first probe set and a second probe set with a genomic DNA sample, comprising a test and reference sample, under hybridisation conditions, wherein:
(i) the first probe set, for the detection of copy number variation by array CGH, comprises a plurality of hybridisation probes substantially complementary to a plurality of target nucleotide sequences in the nucleic acid sample; and(ii) the second probe set comprises one or more pair(s) of hybridisation probes comprising a first allele probe and a second allele probe, wherein the probes are 50-70 nucleotides in length comprising a linker sequence of up to 30 nucleotides in length for one or more of
a SNP positionan INDEL positiona VNTR positiona transposon position wherein the pair(s) of probes differ in sequence such that a nucleic acid target present in the sample can differentially hybridise to the two probes depending onthe nucleotide at the SNP position,the sequence at the INDEL positionthe number of tandem repeats at the VNTR positionthe presence or absence of a transposon at the transposon position wherein a probe's nucleotide at the SNP position is not its 3′ terminal nucleotide; (b) comparing the amount of test sample and reference sample hybridised to the hybridisation probes of the first probe set; (c) comparing the amount of test sample hybridized to the first allele probe and the second allele probe of the second probe set; and (d) using the data obtained in steps (b) and (c) to determine both the copy number of at least one locus and one or more of
at least one SNP in the genomic DNA sampleat least one INDEL in the genomic DNA sampleat least one VNTR in the genomic DNA sampleat least one transposon in the genomic DNA sample.