CUHK Passions and Pursuits

24 P rof. Dennis Lo is perhaps best known for his discovery that the DNA of an unborn fetus could be found in the blood plasma of its pregnant mother. He went on to develop a new method for the prenatal testing of Down syndrome which averted the risk of miscarriage inherent in traditional invasive methods. His pioneering work has made possible a new generation of non-invasive tests. In collaboration with Prof. Rossa Chiu and Prof. Allen Chan , he made a breakthrough by showing that the entire fetal genome is represented in maternal plasma. The next step of devising a non-invasive fetal genome scan was challenging, as fetal DNA molecules, which account for only about 10% of the DNA in the maternal plasma, are highly fragmented. Constructing the fetus’s genetic profile from these fragments would be tantamount to assembling a million-piece jigsaw puzzle. Professor Lo said, ‘To make matters worse, these fetal DNA molecules in the mother’s blood plasma are drifting in an ocean of maternal DNA molecules. This is like adding in tens of millions of pieces from another jigsaw puzzle and then trying to re-assemble the first one.’ To overcome this, the CUHK research team sequenced nearly four billion DNA fragments from a maternal blood sample, which was equivalent to some 65-fold coverage of the human genome. They then constructed separate genetic maps that the fetus had inherited from the father and from the mother. By combining the paternally-inherited and maternally-inherited genetic maps, they were able to arrive at a genomic map of the fetus. They then used this map to confirm that, in the test case in point, the fetus was a