Maddocks Deborah G, Alberry Medhat S, Attilakos George, Madgett Tracey E, Choi Kin, Soothill Peter W, Avent Neil D
Centre for Research in Biomedicine, Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
Biochem Soc Trans. 2009 Apr;37(Pt 2):460-5. doi: 10.1042/BST0370460.
After the revolutionary detection of ffDNA (free fetal DNA) in maternal circulation by real-time PCR in 1997 and advances in molecular techniques, NIPD (non-invasive prenatal diagnosis) is now a clinical reality. Non-invasive diagnosis using ffDNA has been implemented, allowing the detection of paternally inherited alleles, sex-linked conditions and some single-gene disorders and is a viable indicator of predisposition to certain obstetric complications [e.g. PET (pre-eclampsia)]. To date, the major use of ffDNA genotyping in the clinic has been for the non-invasive detection of the pregnancies that are at risk of HDFN (haemolytic disease of the fetus and newborn). This has seen numerous clinical services arising across Europe and many large-scale NIPD genotyping studies taking place using maternal plasma. Because of the interest in performing NIPD and the speed at which the research in this area was developing, the SAFE (Special Non-Invasive Advances in Fetal and Neonatal Evaluation) NoE (Network of Excellence) was founded. The SAFE project was set up to implement routine, cost-effective NIPD and neonatal screening through the creation of long-term partnerships within and beyond the European Community and has played a major role in the standardization of non-invasive RHD genotyping. Other research using ffDNA has focused on the amount of ffDNA present in the maternal circulation, with a view to pre-empting various complications of pregnancy. One of the key areas of interest in the non-invasive arena is the prenatal detection of aneuploid pregnancies, particularly Down's syndrome. Owing to the high maternal DNA background, detection of ffDNA from maternal plasma is very difficult; consequently, research in this area is now more focused on ffRNA to produce new biomarkers.
1997年通过实时聚合酶链反应在母体循环中革命性地检测到游离胎儿DNA（ffDNA）以及分子技术取得进展之后，非侵入性产前诊断（NIPD）如今已成为临床现实。利用ffDNA进行的非侵入性诊断已得以实施，能够检测父系遗传等位基因、性连锁疾病和一些单基因疾病，并且是某些产科并发症[例如子痫前期（PET）]易感性的一个可行指标。迄今为止，ffDNA基因分型在临床上的主要用途一直是对有胎儿和新生儿溶血病（HDFN）风险的妊娠进行非侵入性检测。这在欧洲催生了众多临床服务，并且开展了许多使用母体血浆的大规模NIPD基因分型研究。由于对开展NIPD的兴趣以及该领域研究的发展速度，成立了胎儿和新生儿评估特殊非侵入性进展（SAFE）卓越网络（NoE）。SAFE项目的设立旨在通过在欧洲共同体内外建立长期伙伴关系来实施常规、具有成本效益的NIPD和新生儿筛查，并且在非侵入性RHD基因分型的标准化方面发挥了重要作用。其他利用ffDNA的研究聚焦于母体循环中存在的ffDNA数量，以期预防各种妊娠并发症。非侵入性领域的一个关键关注领域是对非整倍体妊娠，尤其是唐氏综合征进行产前检测。由于母体DNA背景较高，从母体血浆中检测ffDNA非常困难；因此，该领域的研究现在更多地聚焦于ffRNA以产生新的生物标志物。
