NONINVASIVELY DETERMINING A FETAL GENOTYPE AT A MATERNAL HETEROZYGOUS LOCUS

摘要

Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT). 4197657 2 (GHMatters) P83123.AU.3 Dilute Sample and 110 put in wells 120 Carry out PCR on each well 130 Identify markers of alleles 140 identify wells with marker of only particular allele 150 Determine number of informative wells Determine proportion of informative wells contributed by the allele with more positive wells 170 Determine whether the value of Pr shows an allelic imbalance