Array-based methods for analysing mixed samples using differently labelled allele-specific probes

Abstract

This disclosure provides methods and systems useful in array-based analysis of mixed nucleic acid populations, including for multiplex genotyping of a mixed nucleic acid sample and for detecting differences in copy number of a target polynucleotide and/or a target chromosome (e.g., microdeletions, duplications and aneuploidies). The disclosure also provides methods and systems useful in the diagnosis of genetic abnormalities in a mixed nucleic acid population taken non-invasively from an organism, such as a sample of blood, plasma, serum, urine stool or saliva. The disclosed methods and systems find use in multiple applications, including prenatal testing and cancer diagnostics. The disclosure is based on the hybridisation of amplified fragments from the sample, e.g. a maternal sample, which may employ molecular inversion probes MIP to an oligonucleotide array and the detection of the alleles based on different signals from the different alleles of the SNP. The disclosure also discloses how the determination of the allele ratio may be used in the determination of fetal and maternal CNVs, e.g. aneuploidies.