Array-based methods for analysing mixed samples using different allele-specific labels, in particular for detection of fetal aneuploidies

A method for analyzing a biological sample, comprising:

• obtaining the biological sample from a subject who is a pregnant female, the biological sample including nucleic acid of both maternal and fetal origin and containing a target nucleic acid sequence located on a target chromosome, the target nucleic acid sequence containing a polymorphic site for a single nucleotide polymorphism (SNP), the SNP being associated with a first allelic variant (“A allele”) and a second allelic variant (“B allele”), wherein the polymorphic site of the SNP can be homozygous for the A allele (“AA”), homozygous for the B allele (“BB”) or heterozygous (“AB”);
• generating a population of nucleic acid fragments containing or derived from the target nucleic acid sequence;
• conducting a first assay comprising:
• (a) contacting the population of nucleic acid fragments with an oligonucleotide array containing a plurality of first oligonucleotide probes configured to hybridize to the first allelic variant of the target nucleic acid sequence containing the polymorphic site of the SNP and a plurality of second oligonucleotide probes configured to hybridize to the second allelic variant of the target nucleic acid sequence containing the polymorphic site of the SNP;
• and
• (b) detecting, using a detector, first signals indicating hybridization of one or more of the first oligonucleotide probes to one or more nucleic acid fragments of the population containing the first allelic variant of the SNP and second signals indicating hybridization of one or more of the second oligonucleotide probes to one or more nucleic acid fragments of the population containing the second allelic variant of the SNP, wherein the detector has a first and a second detection channel, and the method includes detecting the first signals in the first channel and the second signals in the second channel, wherein the first signals in the first channel indicate the amount of A allele present in the nucleic acid population and the second signals indicate the amount of B allele present in the nucleic acid population;
• and
• determining the copy number of the target chromosome in the fetus by determining a ratio of a first value to a second value.