Detecting fetal chromosomal abnormalities using tandem single nucleotide polymorphisms

1. A method of determining the presence or absence of a fetal chromosomal aneuploidy, comprising:

providing a composition that comprises isolated or purified maternal and fetal nucleic acids molecules from a maternal sample;

determining sets of tandem single nucleotide polymorphisms present in specific chromosomes;

producing amplicons from the composition comprising the determined sets of tandem single nucleotide polymorphisms;

identifying produced amplicons comprising at least 3 different haplotypes of at least one tandem single nucleotide polymorphism (SNP), wherein the single nucleotide polymorphisms in the tandem SNP are at most 250 basepairs apart, and wherein 2 of the 3 haplotypes are present in the maternal nucleic acids and wherein 1 of the 3 haplotypes is not present in the maternal nucleic acids;

quantifying the amount of each of the identified amplicons produced from the composition and comprising the 3 different haplotypes;

comparing the quantified amounts of each amplicon to one another;

comparing the tandem SNPs present in the amplicons so as to identify the chromosomes from which the amplicons are produced;

and

determining whether the fetus has a chromosomal aneuploidy based on the compared quantified amounts of amplicons in the composition.

2. The method of claim 1 , wherein the single nucleotide polymorphisms in the tandem SNP are at most 150 basepairs apart.

3. The method of claim 1 , wherein the single nucleotide polymorphisms in the tandem SNP are at most 100 basepairs apart.

4. The method of claim 1 , wherein the chromosomal aneuploidy is trisomy 13, trisomy 18 or trisomy 21.

5. The method of claim 1 , wherein the produced amplicons comprise at least one of SEQ ID NOs: 1-357.

6. The method of claim 1 , wherein the amplicons are quantified using sequencing.

7. The method of claim 1 , wherein the amplicons are detected using constant denaturant capillary electrophoresis.

8. The method of claim 1 , wherein the amplicons are produced using high-fidelity PCR.

9. The method of claim 8 , further comprising:

separating the amplicons by constant denaturant capillary electrophoresis (CDCE), wherein the amplicons comprising the 3 different haplotypes identified in the identifying step are resolved as 3 peaks in an electropherogram obtained from the CDCE separation, and

wherein quantifying the amount of each of the amplicons comprising the 3 haplotypes comprises measuring peak areas of the 3 resolved peaks in the electropherogram, wherein the 3 resolved peak areas represent the amounts of amplicons.