It has been shown that by the end of the first trimester of pregnancy, a small but significant portion of DNA extracted from maternal plasma is of fetal origin. This knowledge has been utilized for the development of clinical diagnostic assays that are widely used outside the USA for the minimally invasive prenatal determination of, for example, fetal Rhesus antigen status. Such assays that enable the detection of paternally inherited fetal alleles are relatively straightforward, because the fetal sequence of interest is unique to the father and is therefore not masked by any identical maternal alleles. By contrast, maternally inherited traits, including the majority of common human aneuploidies such as trisomy 21, are much harder to detect in plasma because of the overwhelming background of endogenous maternal sequences that are identical to the fetal target alleles. One way to ‘see’ fetal DNA past the veil of maternal genomic DNA is to utilize methods that can selectively amplify or enrich fetal alleles...