INFORMATICS ENHANCED ANALYSIS OF FETAL SAMPLES SUBJECT TO MATERNAL CONTAMINATION

摘要

The invention provides methods for chromosome copy number calling on genetic samples, such as fetal samples subject to contamination from maternal DNA. The present disclosure provides methods for determining the ploidy status of a chromosome in a fetus (such as a gestating fetus or a POC sample) from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. In some embodiments, the ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.