RISK CALCULATION FOR EVALUATION OF FETAL ANEUPLOIDY

摘要

The present invention provides processes for determining accurate risk probabilities for fetal aneuploidies. Specifically, the invention provides non-invasive evaluation of genomic variations through chromosome-selective sequencing and non-host fraction data analysis of maternal samples.

主权项

1. A method to calculate a risk that a first fetal chromosome in a maternal sample comprising maternal and fetal nucleic acids is aneuploid, comprising:
designing sequence-specific oligonucleotide probes directed to a plurality of non-polymorphic loci on each of at least a first and second chromosome; designing sequence-specific oligonucleotide probes directed to a plurality of polymorphic loci on at least a third chromosome; amplifying the plurality of non-polymorphic and polymorphic loci using the sequence-specific oligonucleotide probes; determining a number of each non-polymorphic locus on the at least first and second chromosomes; determining a number of alleles at each polymorphic locus on the at least third chromosome; estimating a chromosome frequency for the at least first and second chromosomes based on the number of non-polymorphic loci on the at least the first and second chromosomes; calculating a fetal nucleic acid proportion in the maternal sample based on the number of alleles at the polymorphic loci; determining whether the fetal nucleic acid proportion in the maternal sample is adequate to reliably perform analysis; calculating a value of likelihood that the first fetal chromosome is disomic using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes; calculating a value of likelihood that the first fetal chromosome is aneuploid using the fetal nucleic acid proportion to adjust the estimated chromosome frequency of the first and second chromosomes; and calculating the risk of a fetal aneuploidy of the first fetal chromosome by comparing the values of likelihood to a first mathematic model assuming a disomic first fetal chromosome and a second mathematic model assuming an aneuploid first fetal chromosome.