Skip to main content
SpringerLink
Log in

Noninvasive Prenatal Diagnosis Using Next-Generation Sequencing

  • Chapter
  • First Online:
Next Generation Sequencing

  • 5293 Accesses

Abstract

Noninvasive prenatal diagnosis could be carried out by analyzing cell-free fetal DNA in the plasma of pregnant women. The clinical applications of circulating fetal DNA have been continuously expanded due to the advancement of molecular detection technology. Next-generation sequencing has provided a powerful means to comprehensively analyze cell-free DNA fragments in maternal plasma. Using this technology, such cell-free DNA fragments can be qualitatively and quantitatively analyzed precisely. The application of next-generation sequencing on maternal plasma DNA analysis has allowed researchers to noninvasively detect fetal chromosome abnormalities with high accuracy. The fetal mutational and polymorphic status could also be revealed in a genome-wide scale. Hence, next-generation sequencing would be expected to play an increasingly important role in noninvasive prenatal investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

SNP:

Single nucleotide polymorphism

NGS:

Next-generation sequencing

GC:

Guanine and cytosine

fetal %:

Fractional fetal DNA concentration

References

  1. Morris JK, Waters JJ, de Souza E (2012) The population impact of screening for Down syndrome: audit of 19 326 invasive diagnostic tests in England and Wales in 2008. Prenat Diagn 32:596–601

    Article  PubMed  Google Scholar 

  2. Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350:485–487

    Article  PubMed  CAS  Google Scholar 

  3. Devaney SA, Palomaki GE, Scott JA, Bianchi DW (2011) Noninvasive fetal sex determination using cell-free fetal DNA: a systematic review and meta-analysis. JAMA 306:627–636

    Article  PubMed  CAS  Google Scholar 

  4. Lun FMF, Chiu RWK, Chan KCA, Leung TY, Lau TK, Lo YMD (2008) Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin Chem 54:1664–1672

    Article  PubMed  CAS  Google Scholar 

  5. Chim SSC, Tong YK, Chiu RWK, Lau TK, Leung TN, Chan LY, Oudejans CB, Ding C, Lo YMD (2005) Detection of the placental epigenetic signature of the maspin gene in maternal plasma. Proc Natl Acad Sci USA 102:14753–14758

    Article  PubMed  CAS  Google Scholar 

  6. Chan KCA, Ding C, Gerovassili A, Yeung SW, Chiu RWK, Leung TN, Lau TK, Chim SSC, Chung GTY, Nicolaides KH, Lo YMD (2006) Hypermethylated RASSF1A in maternal plasma: a universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem 52:2211–2218

    Article  PubMed  CAS  Google Scholar 

  7. Lo YMD, Chiu RWK (2012) Genomic analysis of fetal nucleic acids in maternal blood. Annu Rev Genomics Hum Genet 13:285–306

    Article  PubMed  CAS  Google Scholar 

  8. Finning K, Martin P, Daniels G (2004) A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using free fetal DNA in maternal plasma. Ann N Y Acad Sci 1022:119–123

    Article  PubMed  CAS  Google Scholar 

  9. Chiu RWK, Lo YMD (2012) Noninvasive prenatal diagnosis empowered by high-throughput sequencing. Prenat Diagn 32:401–406

    Article  PubMed  CAS  Google Scholar 

  10. Lo YMD, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM (1998) Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 62:768–775

    Article  PubMed  CAS  Google Scholar 

  11. Tong YK, Ding C, Chiu RWK, Gerovassili A, Chim SSC, Leung TY, Leung TN, Lau TK, Nicolaides KH, Lo YMD (2006) Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: Theoretical and empirical considerations. Clin Chem 52:2194–2202

    Article  PubMed  CAS  Google Scholar 

  12. Lo YMD, Tsui NBY, Chiu RWK, Lau TK, Leung TN, Heung MM, Gerovassili A, Jin Y, Nicolaides KH, Cantor CR, Ding C (2007) Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 13:218–223

    Article  PubMed  CAS  Google Scholar 

  13. Tong YK, Chiu RWK, Akolekar R, Leung TY, Lau TK, Nicolaides KH, Lo YMD (2010) Epigenetic-genetic chromosome dosage approach for fetal trisomy 21 detection using an autosomal genetic reference marker. PLoS One 5:e15244

    Article  PubMed  CAS  Google Scholar 

  14. Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC (2011) Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 17:510–513

    Article  PubMed  CAS  Google Scholar 

  15. Tsaliki E, Papageorgiou EA, Spyrou C, Koumbaris G, Kypri E, Kyriakou S, Sotiriou C, Touvana E, Keravnou A, Karagrigoriou A, Lamnissou K, Velissariou V, Patsalis PC (2012) MeDIP real-time qPCR of maternal peripheral blood reliably identifies trisomy 21. Prenat Diagn 32:996–1001

    Article  PubMed  CAS  Google Scholar 

  16. Tong YK, Chiu RW, Chan KC, Leung TY, Lo YM (2012) Technical concerns about immunoprecipitation of methylated fetal DNA for noninvasive trisomy 21 diagnosis. Nat Med 18:1327–1328

    Article  PubMed  CAS  Google Scholar 

  17. Patsalis PC (2012) Reply to: technical concerns about immunoprecipitation of methylated fetal DNA for noninvasive trisomy 21 diagnosis. Nat Med 18:1328–1329

    Article  CAS  Google Scholar 

  18. Lo YMD, Lun FMF, Chan KCA, Tsui NBY, Chong KC, Lau TK, Leung TY, Zee BC, Cantor CR, Chiu RWK (2007) Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc Natl Acad Sci USA 104:13116–13121

    Article  PubMed  CAS  Google Scholar 

  19. Chiu RWK, Chan KCA, Gao Y, Lau VYM, Zheng W, Leung TY, Foo CH, Xie B, Tsui NBY, Lun FMF, Zee BC, Lau TK, Cantor CR, Lo YMD (2008) Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 105:20458–20463

    Article  PubMed  CAS  Google Scholar 

  20. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR (2008) Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 105:16266–16271

    Article  PubMed  CAS  Google Scholar 

  21. Chiu RWK, Akolekar R, Zheng YWL, Leung TY, Sun H, Chan KCA, Lun FMF, Go AT, Lau ET, To WW, Leung WC, Tang RY, Au-Yeung SK, Lam H, Kung YY, Zhang X, van Vugt JM, Minekawa R, Tang MH, Wang J, Oudejans CB, Lau TK, Nicolaides KH, Lo YMD (2011) Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 342:c7401

    Article  PubMed  Google Scholar 

  22. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, Dean J, Tang L, Hutchison D, Lu T, Wang H, Angkachatchai V, Oeth P, Cantor CR, Bombard A, van den Boom D (2011) Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 204(205):e1–e11

    Google Scholar 

  23. Sehnert AJ, Rhees B, Comstock D, de Feo E, Heilek G, Burke J, Rava RP (2011) Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem 57:1042–1049

    Article  PubMed  CAS  Google Scholar 

  24. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA (2011) DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 13:913–920

    Article  PubMed  CAS  Google Scholar 

  25. Lau TK, Chen F, Pan X, Pooh RK, Jiang F, Li Y, Jiang H, Li X, Chen S, Zhang X (2012) Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing. J Matern Fetal Neonatal Med 25:1370–1374

    Article  PubMed  CAS  Google Scholar 

  26. Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP (2012) Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 119:890–901

    Article  PubMed  CAS  Google Scholar 

  27. Chen EZ, Chiu RWK, Sun H, Akolekar R, Chan KCA, Leung TY, Jiang P, Zheng YWL, Lun FMF, Chan LYS, Jin Y, Go AT, Lau ET, To WW, Leung WC, Tang RY, Au-Yeung SK, Lam H, Kung YY, Zhang X, van Vugt JM, Minekawa R, Tang MH, Wang J, Oudejans CB, Lau TK, Nicolaides KH, Lo YMD (2011) Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 6:e21791

    Article  PubMed  CAS  Google Scholar 

  28. Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA (2012) DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med 14:296–305

    Article  PubMed  CAS  Google Scholar 

  29. Lun FMF, Jin YY, Sun H, Leung TY, Lau TK, Chiu RWK, Lo YMD (2011) Noninvasive prenatal diagnosis of a case of Down syndrome due to robertsonian translocation by massively parallel sequencing of maternal plasma DNA. Clin Chem 57:917–919

    Article  PubMed  CAS  Google Scholar 

  30. Jensen TJ, Dzakula Z, Deciu C, van den Boom D, Ehrich M (2012) Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma. Clin Chem 58:1148–1151

    Article  PubMed  CAS  Google Scholar 

  31. Peters D, Chu T, Yatsenko SA, Hendrix N, Hogge WA, Surti U, Bunce K, Dunkel M, Shaw P, Rajkovic A (2011) Noninvasive prenatal diagnosis of a fetal microdeletion syndrome. N Engl J Med 365:1847–1848

    Article  PubMed  CAS  Google Scholar 

  32. Canick JA, Kloza EM, Lambert-Messerlian GM, Haddow JE, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE (2012) DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn 32:730–734

    Article  PubMed  CAS  Google Scholar 

  33. Lo YMD, Chan KCA, Sun H, Chen EZ, Jiang P, Lun FMF, Zheng YW, Leung TY, Lau TK, Cantor CR, Chiu RWK (2010) Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2:61ra91

    Google Scholar 

  34. Kitzman JO, Snyder MW, Ventura M, Lewis AP, Qiu R, Simmons LE, Gammill HS, Rubens CE, Santillan DA, Murray JC, Tabor HK, Bamshad MJ, Eichler EE, Shendure J (2012) Noninvasive whole-genome sequencing of a human fetus. Sci Transl Med 4:137ra176

    Google Scholar 

  35. van den Oever JM, Balkassmi S, Verweij EJ, van Iterson M, van Scheltema PN, Oepkes D, van Lith JM, Hoffer MJ, den Dunnen JT, Bakker E, Boon EM (2012) Single molecule sequencing of free DNA from maternal plasma for noninvasive trisomy 21 detection. Clin Chem 58:699–706

    Article  PubMed  Google Scholar 

  36. Schadt EE, Turner S, Kasarskis A (2010) A window into third-generation sequencing. Hum Mol Genet 19:R227–R240

    Article  PubMed  CAS  Google Scholar 

  37. Lun FMF, Tsui NBY, Chan KCA, Leung TY, Lau TK, Charoenkwan P, Chow KCK, Lo WY, Wanapirak C, Sanguansermsri T, Cantor CR, Chiu RWK, Lo YMD (2008) Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. Proc Natl Acad Sci USA 105:19920–19925

    Article  PubMed  CAS  Google Scholar 

  38. Jiang P, Chan KCA, Liao GJW, Zheng YW, Leung TY, Chiu RWK, Lo YMD, Sun H (2012) FetalQuant: deducing fractional fetal DNA concentration from massively parallel sequencing of DNA in maternal plasma. Bioinformatics. doi:10.1093/bioinformatics/bts549

    Google Scholar 

  39. Liao GJW, Lun FMF, Zheng YW, Chan KCA, Leung TY, Lau TK, Chiu RWK, Lo YMD (2011) Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin Chem 57:92–101

    Article  PubMed  CAS  Google Scholar 

  40. Liao GJW, Chan KCA, Jiang P, Sun H, Leung TY, Chiu RWK, Lo YMD (2012) Noninvasive prenatal diagnosis of fetal trisomy 21 by allelic ratio analysis using targeted massively parallel sequencing of maternal plasma DNA. PLoS One 7:e38154

    Article  PubMed  CAS  Google Scholar 

  41. Lam KWG, Jiang P, Liao GJW, Chan KCA, Leung TY, Chiu RWK, Lo YMD (2012) Noninvasive prenatal diagnosis of monogenic diseases by targeted massively parallel sequencing of maternal plasma: application to beta Thalassemia. Clin Chem. doi:10.1373/clinchem.2012.189589

    PubMed  Google Scholar 

  42. Sparks AB, Struble CA, Wang ET, Song K, Oliphant A (2012) Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 206(319):e1–e9

    PubMed  Google Scholar 

  43. Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH (2012) Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol 206(322):e1–e5

    PubMed  Google Scholar 

  44. Kalousek DK, Vekemans M (1996) Confined placental mosaicism. J Med Genet 33:529–533

    Article  PubMed  CAS  Google Scholar 

  45. Feuk L, Carson AR, Scherer SW (2006) Structural variation in the human genome. Nat Rev Genet 7:85–97

    Article  PubMed  CAS  Google Scholar 

  46. Chitty LS, Hill M, White H, Wright D, Morris S (2012) Noninvasive prenatal testing for aneuploidy-ready for prime time? Am J Obstet Gynecol 206:269–275

    Article  PubMed  Google Scholar 

  47. Deans Z, Newson AJ (2012) Ethical considerations for choosing between possible models for using NIPD for aneuploidy detection. J Med Ethics 38:614–618

    Article  PubMed  Google Scholar 

  48. Greely HT (2011) Get ready for the flood of fetal gene screening. Nature 469:289–291

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Li Ka Shing Institute of Health Sciences and Department of Chemical Pathology, Centre for Research into Circulating Fetal Nucleic Acids, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China

    Nancy Bo Yin Tsui & Yuk Ming Dennis Lo

Authors
  1. Nancy Bo Yin Tsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuk Ming Dennis Lo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuk Ming Dennis Lo .

Editor information

Editors and Affiliations

  1. , Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Tsui, N.B.Y., Lo, Y.M.D. (2013). Noninvasive Prenatal Diagnosis Using Next-Generation Sequencing. In: Wong, LJ. (eds) Next Generation Sequencing. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7001-4_13

Download citation

Publish with us

Policies and ethics

Search

Navigation