Clinical applications of maternal plasma fetal DNA analysis: translating the fruits of 15 years of research

• Published in: Clinical chemistry and laboratory medicine Vol. 51; no. 1; pp. 197 - 204
• Main Authors: Kwun Chiu, Rossa Wai, Dennis Lo, Yuk Ming
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.01.2013; Walter De Gruyter & Company
• Subjects: Amniocentesis; Aneuploidy; Blood groups; cell-free fetal DNA; Deoxyribonucleic acid; Diagnosis; DNA; DNA - blood; DNA - genetics; DNA - history; Down syndrome; Fetuses; Genetic disorders; Genomes; Genotyping; History, 20th Century; History, 21st Century; Humans; maternal plasma DNA; next-generation sequencing; non-invasive prenatal diagnosis; Plasma; Prenatal diagnosis; Prenatal Diagnosis - history; Prenatal Diagnosis - methods; Research - history; Sampling; Villus
• ISSN: 1434-6621; 1437-4331
• DOI: 10.1515/cclm-2012-0601

The collection of fetal genetic materials is required for the prenatal diagnosis of fetal genetic diseases. The conventional methods for sampling fetal genetic materials, such as amniocentesis and chorionic villus sampling, are invasive in nature and are associated with a risk of fetal miscarriage. For decades, scientists had been pursuing studies with goals to develop non-invasive methods for prenatal diagnosis. In 1997, the existence of fetal derived cell-free DNA molecules in plasma of pregnant women was first demonstrated. This finding provided a new source of fetal genetic material that could be obtained safely through the collection of a maternal blood sample and provided a new avenue for the development of non-invasive prenatal diagnostic tests. Now 15 years later, the diagnostic potential of circulating fetal DNA analysis has been realized. Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection. Most recently, research groups have succeeded in decoding the entire fetal genome from maternal plasma DNA analysis which paved the way for the achievement of non-invasive prenatal diagnosis of many single gene diseases. A paradigm shift in the practice of prenatal diagnosis has begun.