Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

Application of digital polymerase chain reaction technology for noninvasive prenatal test

  • Received : 2015.11.09
  • Accepted : 2015.12.09
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Recently, noninvasive prenatal test (NIPT) has been adopted as a primary screening tool for fetal chromosomal aneuploidy. The principle of NIPT lies in isolating the fetal fraction of cell-free DNA in maternal plasma and analyzing it with bioinformatic tools to measure the amount of gene from the target chromosome, such as chromosomes 21, 18, and 13. NIPT will contribute to decreasing the need for unnecessary invasive procedures, including amniocentesis and chorionic villi sampling, for confirming fetal aneuploidy because of its higher positive predictive value than that of the conventional prenatal screening method. However, its greater cost than that of the current antenatal screening protocol may be an obstacle to the adoption of this innovative technique in clinical practice. Digital polymerase chain reaction (dPCR) is a novel approach for detecting and quantifying nucleic acid. dPCR provides real-time diagnostic advantages with higher sensitivity, accuracy, and absolute quantification than conventional quantitative PCR. Since the groundbreaking discovery that fetal cell-free nucleic acid exists in maternal plasma was reported, dPCR has been used for the quantification of fetal DNA and for screening for fetal aneuploidy. It has been suggested that dPCR will decrease the cost by targeting specific sequences in the target chromosome, and dPCR-based noninvasive testing will facilitate progress toward the implementation of a noninvasive approach for screening for trisomy 21, 18, and 13. In this review, we highlight the principle of dPCR and discuss its future implications in clinical practice.

Keywords

References

  1. Bili C, Divane A, Apessos A, Konstantinos T, Apostolos A, Ioannis B, et al. Prenatal diagnosis of common aneuploidies using quantitative fluorescent PCR. Prenat Diagn 2002;22:360-5. https://doi.org/10.1002/pd.301
  2. Tepperberg J, Pettenati MJ, Rao PN, Lese CM, Rita D, Wyandt H, et al. Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2-year multi-center retrospective study and review of the literature. Prenat Diagn 2001;21:293-301. https://doi.org/10.1002/pd.57
  3. Cuckle HS, van Lith JM. Appropriate biochemical parameters in firsttrimester screening for Down syndrome. Prenat Diagn 1999;19:505-12. https://doi.org/10.1002/(SICI)1097-0223(199906)19:6<505::AID-PD572>3.0.CO;2-6
  4. Hayes A, Batshaw ML. Down syndrome. Pediatr Clin North Am 1993;40:523-35. https://doi.org/10.1016/S0031-3955(16)38548-0
  5. Bianchi D, Larrabee P, Johnson K; assignees. Prenatal diagnosis using cell-free fetal DNA in amniotic fluid. US 10/577,341. 2004, Oct 29.
  6. Rasmussen SA, Wong LY, Yang Q, May KM, Friedman JM. Populationbased analyses of mortality in trisomy 13 and trisomy 18. Pediatrics 2003;111:777-84. https://doi.org/10.1542/peds.111.4.777
  7. Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S. Chromosome 21 and down syndrome: from genomics to pathophysiology. Nat Rev Genet 2004;5:725-38. https://doi.org/10.1038/nrg1448
  8. Desai SS. Down syndrome: a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:279-85. https://doi.org/10.1016/S1079-2104(97)90343-7
  9. Green RF, Devine O, Crider KS, Olney RS, Archer N, Olshan AF, et al; National Birth Defects Prevention Study. Association of paternal age and risk for major congenital anomalies from the National Birth Defects Prevention Study, 1997 to 2004. Ann Epidemiol 2010;20:241-9. https://doi.org/10.1016/j.annepidem.2009.10.009
  10. Goldberg JD, Golbus MS. Chorionic villus sampling. Adv Hum Genet 1988;17:1-25.
  11. Wapner RJ, Jackson L. Chorionic villus sampling. Clin Obstet Gynecol 1988;31:328-44. https://doi.org/10.1097/00003081-198806000-00010
  12. Wegner RD, Toennies H. Chorionic villi sampling. In: Wegner RD, ed. Diagnostic cytogenetics. Berlin: Springer, 1999:231-47.
  13. Alfirevic Z, Mujezinovic F, Sundberg K. Amniocentesis and chorionic villus sampling for prenatal diagnosis (Review). Cochrane Database Syst Rev 2009;1:1-142.
  14. Mujezinovic F, Alfirevic Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007;110:687-94. https://doi.org/10.1097/01.AOG.0000278820.54029.e3
  15. Tongsong T, Wanapirak C, Kunavikatikul C, Sirirchotiyakul S, Piyamongkol W, Chanprapaph P. Cordocentesis at 16-24 weeks of gestation: experience of 1,320 cases. Prenat Diagn 2000;20:224-8. https://doi.org/10.1002/(SICI)1097-0223(200003)20:3<224::AID-PD788>3.0.CO;2-M
  16. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:485-7. https://doi.org/10.1016/S0140-6736(97)02174-0
  17. Pinheiro LB, Coleman VA, Hindson CM, Herrmann J, Hindson BJ, Bhat S, et al. Evaluation of a droplet digital polymerase chain reaction format for DNA copy number quantification. Anal Chem 2012;84:1003-11. https://doi.org/10.1021/ac202578x
  18. Benn P, Cuckle H, Pergament E. Non-invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound Obstet Gynecol 2013;42:15-33.
  19. Kubista M, Andrade JM, Bengtsson M, Forootan A, Jonak J, Lind K, et al. The real-time polymerase chain reaction. Mol Aspects Med 2006;27:95-125. https://doi.org/10.1016/j.mam.2005.12.007
  20. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62:768-75. https://doi.org/10.1086/301800
  21. Eisenstein BI. The polymerase chain reaction. A new method of using molecular genetics for medical diagnosis. N Engl J Med 1990;322:178-83. https://doi.org/10.1056/NEJM199001183220307
  22. Vogelstein B, Kinzler KW. Digital PCR. Proc Natl Acad Sci U S A 1999;96:9236-41. https://doi.org/10.1073/pnas.96.16.9236
  23. Dube S, Qin J, Ramakrishnan R. Mathematical analysis of copy number variation in a DNA sample using digital PCR on a nanofluidic device. PLoS One 2008;3:e2876. https://doi.org/10.1371/journal.pone.0002876
  24. Day E, Dear PH, McCaughan F. Digital PCR strategies in the development and analysis of molecular biomarkers for personalized medicine. Methods 2013;59:101-7. https://doi.org/10.1016/j.ymeth.2012.08.001
  25. Chiu RW, Lo YM. Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal plasma: the coming of age. Semin Fetal Neonatal Med 2011;16:88-93. https://doi.org/10.1016/j.siny.2010.10.003
  26. Kotsopoulou I, Tsoplou P, Mavrommatis K, Kroupis C. Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis. Diagnosis 2015;2:141-58. https://doi.org/10.1515/dx-2015-0002
  27. Twiss P, Hill M, Daley R, Chitty LS. Non-invasive prenatal testing for Down syndrome. Semin Fetal Neonatal Med 2014;19:9-14. https://doi.org/10.1016/j.siny.2013.10.003
  28. Vaiopoulos AG, Athanasoula KC, Papantoniou N, Kolialexi A. Review: advances in non-invasive prenatal diagnosis. In Vivo 2013;27:165-70.
  29. Evans MI, Kilpatrick M. Noninvasive prenatal diagnosis: 2010. Clin Lab Med 2010;30:655-65. https://doi.org/10.1016/j.cll.2010.04.011
  30. Lo YM, Lun FM, Chan KC, Tsui NB, Chong KC, Lau TK, et al. Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc Natl Acad Sci U S A 2007;104:13116-21. https://doi.org/10.1073/pnas.0705765104
  31. Fan HC, Blumenfeld YJ, El-Sayed YY, Chueh J, Quake SR. Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy. Am J Obstet Gynecol 2009;200:543.e1-7. https://doi.org/10.1016/j.ajog.2009.03.002
  32. Evans MI, Wright DA, Pergament E, Cuckle HS, Nicolaides KH. Digital PCR for noninvasive detection of aneuploidy: power analysis equations for feasibility. Fetal Diagn Ther 2012;31:244-7. https://doi.org/10.1159/000337544
  33. Svobodova I, Pazourkova E, Horinek A, Novotna M, Calda P, Korabecna M. Performance of droplet digital PCR in non-invasive fetal RHD genotyping - Comparison with a routine real-time PCR based approach. PLoS One 2015;10:e0142572. https://doi.org/10.1371/journal.pone.0142572
  34. Debrand E, Lykoudi A, Bradshaw E, Allen SK. A non-invasive droplet digital PCR (ddPCR) assay to detect paternal CFTR mutations in the cell-free fetal DNA (cffDNA) of three pregnancies at risk of cystic fibrosis via compound heterozygosity. PLoS One 2015;10:e0142729. https://doi.org/10.1371/journal.pone.0142729
  35. Tsui NB, Hyland CA, Gardener GJ, Danon D, Fisk NM, Millard G, et al. Noninvasive fetal RHD genotyping by microfluidics digital PCR using maternal plasma from two alloimmunized women with the variant RHD(IVS3+1G>A) allele. Prenat Diagn 2013;33:1214-6. https://doi.org/10.1002/pd.4230
  36. Tsui NB, Kadir RA, Chan KC, Chi C, Mellars G, Tuddenham EG, et al. Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA. Blood 2011;117:3684-91. https://doi.org/10.1182/blood-2010-10-310789
  37. Sillence KA, Roberts LA, Hollands HJ, Thompson HP, Kiernan M, Madgett TE, et al. Fetal sex and RHD genotyping with digital PCR demonstrates greater sensitivity than real-time PCR. Clin Chem 2015;61:1399-407. https://doi.org/10.1373/clinchem.2015.239137
  38. Ma J, Li N, Guarnera M, Jiang F. Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights 2013;8:127-36.
  39. Li M, Chen WD, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol 2009;27:858-63. https://doi.org/10.1038/nbt.1559
  40. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 2011;83:8604-10. https://doi.org/10.1021/ac202028g