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China: From a Pregnant Woman’s Blood Sample, Researchers Determine Baby’s Genome

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9 December 2010. CUHK Medicine Faculty the First to Decode Fetal Genomic Map from Maternal Blood. A ground-breaking technology for scanning the entire genome of a fetus non-invasively from a blood sample obtained from its pregnant mother developed by a research team led by Professor Dennis Lo Yuk-ming, Director of the Li Ka Shing Institute of Health Sciences at The Chinese University of Hong Kong (CUHK), was reported in the latest issue of the premier biomedical journal, Science Translational Medicine.In 1997, Professor Dennis Lo and his co-workers discovered the presence of cell-free fetal DNA in maternal blood plasma. This discovery has opened up new possibilities for non-invasive prenatal diagnosis, reducing our reliance on conventional invasive, potentially risky, methods of prenatal diagnosis, e.g. amniocentesis. Since then, this technology has been used by many researchers and diagnostic laboratories around the world, with testing typically focusing on one disorder, e.g. Down syndrome, at a time. The new research reported in Science Translational Medicine represents a quantum jump over the previous state-of-the-art in the field as it allows multiple disorders on a genome-wide scale to be scanned in one test.To investigate if such a test is scientifically possible, Professor Lo and his colleagues had to first demonstrate that the entire fetal genome was present in

maternal blood plasma. After an affirmative result was obtained, the research team then went on to develop the technology needed for a non-invasive fetal genome scan. This task is very challenging because the DNA molecules in blood plasma are highly fragmented. Professor Lo says, “It is like trying to assemble a jigsaw puzzle that has millions of pieces. To make matters worse, the fetal DNA molecules in the pregnant mother’s blood plasma are surrounded by an ocean of maternal DNA molecules. This is similar to adding in tens of millions of pieces from another jigsaw puzzle and then trying to re-assemble the first one.” To achieve this task, the research team sequenced nearly 4 billion DNA fragments from the maternal blood sample. This was equivalent to some 65-fold coverage of the human genome. They then searched the sequencing data for genetic signatures that were only present in the father, but absent in the mother, of the fetus. Taking these signatures together, the team then built a genetic map of sequences that the fetus had inherited from its father. The building of the fetal inheritance map from its mother was much more challenging as fetal DNA represented only some 10% of the DNA in maternal plasma. The remaining 90% consisted of DNA from the mother herself. To solve this problem, the research team had developed a new technology that would allow the minute increases in the concentration of sequences that the fetus had inherited from its mother to be detected in maternal plasma, and thus constructed a fetal inheritance map from the mother.By combining the paternally-inherited and maternally-inherited genetic maps, CUHK researchers were able to arrive at a genomic map of the fetus. The research team then used the map to show that the fetus was a carrier of beta-thalassaemia, a relatively common genetic blood disorder in Southeast Asia. This important

development has laid the foundation for a new generation of prenatal tests that can detect multiple genetic disorders that are common in a particularly geographical area. While this technology is still relatively expensive at present, it is expected that costs will rapidly come down.  Professor Dennis Lo Yuk-ming Professor Dennis Lo is the Professor of Chemical Pathology and Li Ka Shing Professor of Medicine of The Chinese University of Hong Kong. He is also the Associate Dean (Research) of the Faculty of Medicine, the Director of the Li Ka Shing Institute of Health Sciences and an Associate Director of the State Key Laboratory in Oncology in South China. He obtained his B.A. degree from the University of Cambridge and his B.M.B.Ch. degree from the University of Oxford. Following his clinical studies, he pursued a period of postgraduate research, resulting in the award of a D.Phil. degree from Oxford. He received his clinical training in internal medicine and chemical pathology from John Radcliffe Hospital, the teaching hospital of the University of Oxford Clinical School, where he was appointed University Lecturer in Clinical Biochemistry and Honorary Consultant Chemical Pathologist. Prof. Lo is a Fellow of the Royal College of Physicians ( London and Edinburgh) and a Fellow of the Royal College of Pathologists of the U.K. Professor Lo’s main research interests lie in the clinical applications of molecular biology. He is a pioneer in noninvasive prenatal diagnosis using cell-free fetal DNA and RNA in maternal plasma/serum. Professor Lo is also actively pursuing the application of plasma-based molecular technology to the diagnosis and monitoring of nasopharyngeal carcinoma and hepatocellular carcinoma. Professor Lo has produced over 243 publications in international journals. His research is currently supported by the Hong Kong Research Grants Council, the Innovation and Technology Fund,

the Research Fund for the Control of Infectious Diseases (from the Health, Welfare and Food Bureau), the Kadoorie Charitable Foundation and the Li Ka Shing Foundation. Professor Lo is a past President of the Hong Kong Society of Clinical Chemistry. Professor Lo is an Associate Editor of Clinical Chemistry, and serves on the Editorial Boards of American Journal of Hematology, Disease Markers, Prenatal Diagnosis, Chimerism and Fetal Diagnosis and Therapy. News from: The Chinese University of Hong Kong (CUHK)  –  The Chinese University of Hong Kong (CUHK) is a top research intensive university in Hong Kong. It placed 42nd globally  in the 2010 QS World University Rankings and has standing as one of the world’s premier universities ranked in the upper tier.The Chinese University is the only tertiary education institution in Hong Kong with Nobel Prize winners on its faculty, including Chen Ning Yang, James Mirrlees, Robert Alexander Mundell and Charles K. Kao (winner of the 2009 Nobel Prize in Physics). Other eminent thinkers at the university include mathematician Shing-Tung Yau, holder of the prestigious Fields Medal and Veblen Prize, and computational theorist Andrew Yao, winner of the Turing Award.The Chinese University is an officially trilingual campus; its languages of instruction are English, Cantonese, and Mandarin. The school is home to the renowned Yale-China Chinese Language Center. The university has 61 academic departments organized under eight faculties: arts, business administration, education, engineering, social science, medicine, science, and law.Within these 61 departments are 117 undergraduate programs and 247 postgraduate programs.The university’s founders hoped that it would become the bridge that connects China and the West, and to combine tradition with modernity.  GoodNews International

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