1932

Abstract

Noninvasive prenatal testing (NIPT) is accomplished by analysis of circulating cell-free fetal nucleic acids in maternal plasma. The advent of massively parallel sequencing (MPS) has enabled NIPT of chromosomal aneuploidies with unprecedented robustness, and these tests are now widely available for clinical use. Moreover, MPS-based NIPT of subchromosomal deletions/duplications and single-gene disorders has also been achieved, and the number of applications is growing. In addition to specific fetal genetic disorders, the whole fetal genome, transcriptome, and methylome have been revealed by deep sequencing of maternal plasma. The analysis of the fetal transcriptome and methylome may yield valuable information on fetal and maternal health. With continued improvement in sequencing technology and reduction in sequencing costs, the analysis of cell-free nucleic acids would play an increasingly important role in prenatal screening, diagnosis, monitoring, and risk stratification of fetal as well as maternal conditions.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-091014-115715
2016-01-14
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/med/67/1/annurev-med-091014-115715.html?itemId=/content/journals/10.1146/annurev-med-091014-115715&mimeType=html&fmt=ahah

Literature Cited

  1. Lo YM, Corbetta N, Chamberlain PF. 1.  et al. 1997. Presence of fetal DNA in maternal plasma and serum. Lancet 350:485–87 [Google Scholar]
  2. Mujezinovic F, Alfirevic Z. 2.  2007. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet. Gynecol. 110:687–94 [Google Scholar]
  3. Herzenberg LA, Bianchi DW, Schröder J. 3.  et al. 1979. Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting. PNAS 76:1453–55 [Google Scholar]
  4. Lo YM, Tein MS, Lau TK. 4.  et al. 1998. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am. J. Hum. Genet. 62:768–75 [Google Scholar]
  5. Lun FM, Chiu RW, Chan KC. 5.  et al. 2008. Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin. Chem. 54:1664–72 [Google Scholar]
  6. Lo YM, Zhang J, Leung TN. 6.  et al. 1999. Rapid clearance of fetal DNA from maternal plasma. Am. J. Hum. Genet. 64:218–24 [Google Scholar]
  7. Masuzaki H, Miura K, Yoshiura KI. 7.  et al. 2004. Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism. J. Med. Genet. 41:289–92 [Google Scholar]
  8. Alberry M, Maddocks D, Jones M. 8.  et al. 2007. Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenat. Diagn. 27:415–18 [Google Scholar]
  9. Rijnders RJ, Van Der Luijt RB, Peters ED. 9.  et al. 2003. Earliest gestational age for fetal sexing in cell-free maternal plasma. Prenat. Diagn. 23:1042–44 [Google Scholar]
  10. Lui YY, Chik KW, Chiu RW. 10.  et al. 2002. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin. Chem. 48:421–27 [Google Scholar]
  11. Lun FM, Chiu RW, Sun K. 11.  et al. 2013. Noninvasive prenatal methylomic analysis by genomewide bisulfite sequencing of maternal plasma DNA. Clin. Chem. 59:1583–94 [Google Scholar]
  12. Chan KC, Zhang J, Hui AB. 12.  et al. 2004. Size distributions of maternal and fetal DNA in maternal plasma. Clin. Chem. 50:88–92 [Google Scholar]
  13. Lo YM, Chan KC, Sun H. 13.  et al. 2010. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci. Transl. Med. 2:61ra91 [Google Scholar]
  14. Lo YM. 14.  2013. Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing. Reprod. Biomed. Online 27:593–98 [Google Scholar]
  15. Chiu RW, Lo YM. 15.  2013. Clinical applications of maternal plasma fetal DNA analysis: translating the fruits of 15 years of research. Clin. Chem. Lab. Med. 51:197–204 [Google Scholar]
  16. Sims D, Sudbery I, Ilott NE. 16.  et al. 2014. Sequencing depth and coverage: key considerations in genomic analyses. Nat. Rev. Genet. 15:121–32 [Google Scholar]
  17. Driscoll DA, Gross SJ. 17.  2009. Screening for fetal aneuploidy and neural tube defects. Professional Practice Guidelines Committee. Genet. Med. 11:818–21 [Google Scholar]
  18. Chiu RW, Chan KC, Gao Y. 18.  et al. 2008. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. PNAS 105:20458–63 [Google Scholar]
  19. Fan HC, Blumenfeld YJ, Chitkara U. 19.  et al. 2008. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. PNAS 105:16266–71 [Google Scholar]
  20. Liao GJ, Lun FM, Zheng YW. 20.  et al. 2011. Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin. Chem. 57:92–101 [Google Scholar]
  21. Liao GJ, Chan KC, Jiang P. 21.  et al. 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 [Google Scholar]
  22. Zimmermann B, Hill M, Gemelos G. 22.  et al. 2012. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat. Diagn. 32:1233–41 [Google Scholar]
  23. Sparks AB, Struble CA, Wang ET. 23.  et al. 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. 206:319e1–9 [Google Scholar]
  24. Sparks AB, Wang ET, Struble CA. 24.  et al. 2012. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat. Diagn. 32:3–9 [Google Scholar]
  25. Juneau K, Bogard PE, Huang S. 25.  et al. 2014. Microarray-based cell-free DNA analysis improves noninvasive prenatal testing. Fetal Diagn. Ther. 36:282–86 [Google Scholar]
  26. Chiu RW, Akolekar R, Zheng YW. 26.  et al. 2011. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 342:c7401 [Google Scholar]
  27. Sehnert AJ, Rhees B, Comstock D. 27.  et al. 2011. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin. Chem. 57:1042–49 [Google Scholar]
  28. Palomaki GE, Deciu C, Kloza EM. 28.  et al. 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 [Google Scholar]
  29. Ehrich M, Deciu C, Zwiefelhofer T. 29.  et al. 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.e1–11 [Google Scholar]
  30. Palomaki GE, Kloza EM, Lambert-Messerlian GM. 30.  et al. 2011. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet. Med. 13:913–20 [Google Scholar]
  31. Bianchi DW, Platt LD, Goldberg JD. 31.  et al. 2012. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet. Gynecol. 119:890–901 [Google Scholar]
  32. Norton ME, Brar H, Weiss J. 32.  et al. 2012. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 207:137.e1–8 [Google Scholar]
  33. Nicolaides KH, Syngelaki A, Gil M. 33.  et al. 2013. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat. Diagn. 33:575–79 [Google Scholar]
  34. Gil MM, Akolekar R, Quezada MS. 34.  et al. 2014. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis. Fetal Diagn. Ther. 35:156–73 [Google Scholar]
  35. Gil MM, Quezada MS, Revello R. 35.  et al. 2015. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet. Gynecol. 45:249–66 [Google Scholar]
  36. Wegrzyn P, Faro C, Falcon O. 36.  et al. 2005. Placental volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects. Ultrasound Obstet. Gynecol. 26:28–32 [Google Scholar]
  37. Benn P, Borrell A, Crossley J. 37.  et al. 2011. Aneuploidy screening: a position statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, January 2011. Prenat. Diagn. 31:519–22 [Google Scholar]
  38. 38. American College of Obstetricians and Gynecologists Committee on Genetics 2012. Committee Opinion No. 545: noninvasive prenatal testing for fetal aneuploidy. Obstet. Gynecol. 120:1532–4 [Google Scholar]
  39. Devers PL, Cronister A, Ormond KE. 39.  et al. 2013. Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors. J. Genet. Couns. 22:291–95 [Google Scholar]
  40. Gregg AR, Gross SJ, Best RG. 40.  et al. 2013. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet. Med. 15:395–98 [Google Scholar]
  41. Langlois S, Brock JA, Wilson RD. 41.  et al. 2013. Current status in non-invasive prenatal detection of Down syndrome, trisomy 18, and trisomy 13 using cell-free DNA in maternal plasma. J. Obstet. Gynaecol. Can. 35:177–83 [Google Scholar]
  42. Hudecova I, Sahota D, Heung MM. 42.  et al. 2014. Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies. PLoS ONE 9:e88484 [Google Scholar]
  43. Nicolaides KH, Syngelaki A, Ashoor G. 43.  et al. 2012. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am. J. Obstet. Gynecol. 207:374.e1–6 [Google Scholar]
  44. Dan S, Wang W, Ren J. 44.  et al. 2012. Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors. Prenat. Diagn. 32:1225–32 [Google Scholar]
  45. Bianchi DW, Parker RL, Wentworth J. 45.  et al. 2014. DNA sequencing versus standard prenatal aneuploidy screening. N. Engl. J. Med. 370:799–808 [Google Scholar]
  46. Norton ME, Jacobsson B, Swamy GK. 46.  et al. 2015. Cell-free DNA analysis for noninvasive examination of trisomy. N. Engl. J. Med. 372:1589–97 [Google Scholar]
  47. Searle CJ, Smith K, Daniels G. 47.  et al. 2013. Cell-free fetal DNA sex determination identified a maternal SRY gene with a known X chromosome deletion. Prenat. Diagn. 33:612–13 [Google Scholar]
  48. Lau TK, Jiang FM, Stevenson RJ. 48.  et al. 2013. Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service. Prenat. Diagn. 33:602–8 [Google Scholar]
  49. Snyder MW, Simmons LE, Kitzman JO. 49.  et al. 2015. Copy-number variation and false positive prenatal aneuploidy screening results. N. Engl. J. Med. 372:1639–45 [Google Scholar]
  50. Wang Y, Chen Y, Tian F. 50.  et al. 2014. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Clin. Chem. 60:251–59 [Google Scholar]
  51. Pan M, Li FT, Li Y. 51.  et al. 2013. Discordant results between fetal karyotyping and non-invasive prenatal testing by maternal plasma sequencing in a case of uniparental disomy 21 due to trisomic rescue. Prenat. Diagn. 33:598–601 [Google Scholar]
  52. Canick JA, Kloza EM, Lambert-Messerlian GM. 52.  et al. 2012. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat. Diagn. 32:730–34 [Google Scholar]
  53. Leung TY, Qu JZ, Liao GJ. 53.  et al. 2013. Noninvasive twin zygosity assessment and aneuploidy detection by maternal plasma DNA sequencing. Prenat. Diagn. 33:675–81 [Google Scholar]
  54. Qu JZ, Leung TY, Jiang P. 54.  et al. 2013. Noninvasive prenatal determination of twin zygosity by maternal plasma DNA analysis. Clin. Chem. 59:427–35 [Google Scholar]
  55. Peters D, Chu T, Yatsenko SA. 55.  et al. 2011. Noninvasive prenatal diagnosis of a fetal microdeletion syndrome. N. Engl. J. Med. 365:1847–48 [Google Scholar]
  56. Jensen TJ, Dzakula Z, Deciu C. 56.  et al. 2012. Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma. Clin. Chem. 58:1148–51 [Google Scholar]
  57. Yu SC, Jiang P, Choy KW. 57.  et al. 2013. Noninvasive prenatal molecular karyotyping from maternal plasma. PLoS ONE 8:e60968 [Google Scholar]
  58. Srinivasan A, Bianchi DW, Huang H. 58.  et al. 2013. Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. Am. J. Hum. Genet. 92:167–76 [Google Scholar]
  59. Chen S, Lau TK, Zhang C. 59.  et al. 2013. A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing. Prenat. Diagn. 33:584–90 [Google Scholar]
  60. Straver R, Sistermans EA, Holstege H. 60.  et al. 2014. WISECONDOR: detection of fetal aberrations from shallow sequencing maternal plasma based on a within-sample comparison scheme. Nucleic Acids Res. 42:e31 [Google Scholar]
  61. Zhao C, Tynan J, Ehrich M. 61.  et al. 2015. Detection of fetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma. Clin. Chem. 61:608–16 [Google Scholar]
  62. Wapner RJ, Babiarz JE, Levy B. 62.  et al. 2015. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am. J. Obstet. Gynecol. 212:332.e1–9 [Google Scholar]
  63. Slavotinek A. 63.  2012. Microdeletion syndromes. eLS: Citable Reviews in the Life Sciences. Chichester, UK: Wiley http://www.els.net. doi: 10.1002/9780470015902.a0005549.pub2 [Google Scholar]
  64. Lo YM, Hjelm NM, Fidler C. 64.  et al. 1998. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N. Engl. J. Med. 339:1734–38 [Google Scholar]
  65. González-González MC, Trujillo MJ, Rodríguez de Alba M. 65.  et al. 2003. Huntington disease-unaffected fetus diagnosed from maternal plasma using QF-PCR. Prenat. Diagn. 23:232–34 [Google Scholar]
  66. Amicucci P, Gennarelli M, Novelli G, Dallapiccola B. 66.  2000. Prenatal diagnosis of myotonic dystrophy using fetal DNA obtained from maternal plasma. Clin. Chem. 46:301–2 [Google Scholar]
  67. Meaney C, Norbury G. 67.  2009. Noninvasive prenatal diagnosis of early onset primary dystonia I in maternal plasma. Prenat. Diagn. 29:1218–21 [Google Scholar]
  68. Chitty LS, Griffin DR, Meaney C. 68.  et al. 2011. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma. Ultrasound Obstet. Gynecol. 37:283–89 [Google Scholar]
  69. Chitty LS, Khalil A, Barrett AN. 69.  et al. 2013. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat. Diagn. 33:416–23 [Google Scholar]
  70. Chitty LS, Mason S, Barrett AN. 70.  et al. 2015. Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach. Prenat. Diagn. 35656–62
  71. Lun FM, Tsui NB, Chan KC. 71.  et al. 2008. Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. PNAS 105:19920–25 [Google Scholar]
  72. Barrett AN, McDonnell TC, Chan KC, Chitty LS. 72.  2012. Digital PCR analysis of maternal plasma for noninvasive detection of sickle cell anemia. Clin. Chem. 58:1026–32 [Google Scholar]
  73. Tsui NB, Kadir RA, Chan KC. 73.  et al. 2011. Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA. Blood 117:3684–91 [Google Scholar]
  74. Lam KW, Jiang P, Liao GJ. 74.  et al. 2012. Noninvasive prenatal diagnosis of monogenic diseases by targeted massively parallel sequencing of maternal plasma: application to β-thalassemia. Clin. Chem. 58:1467–75 [Google Scholar]
  75. New MI, Tong YK, Yuen T. 75.  et al. 2014. Noninvasive prenatal diagnosis of congenital adrenal hyperplasia using cell-free fetal DNA in maternal plasma. J. Clin. Endocrinol. Metab. 99:E1022–30 [Google Scholar]
  76. Fan HC, Gu W, Wang J. 76.  et al. 2012. Non-invasive prenatal measurement of the fetal genome. Nature 487:320–24 [Google Scholar]
  77. Kitzman JO, Snyder MW, Ventura M. 77.  et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Sci. Transl. Med. 4:137ra76 [Google Scholar]
  78. Chen S, Ge H, Wang X. 78.  et al. 2013. Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing. Genome Med. 5:18 [Google Scholar]
  79. Fan HC, Wang J, Potanina A, Quake SR. 79.  2011. Whole-genome molecular haplotyping of single cells. Nat. Biotechnol. 29:51–57 [Google Scholar]
  80. Kitzman JO, Mackenzie AP, Adey A. 80.  et al. 2011. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nat. Biotechnol. 29:59–63 [Google Scholar]
  81. Peters BA, Kermani BG, Sparks AB. 81.  et al. 2012. Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature 487:190–95 [Google Scholar]
  82. Snyder MW, Simmons LE, Kitzman JO. 82.  et al. 2013. Noninvasive fetal genome sequencing: a primer. Prenat. Diagn. 33:547–54 [Google Scholar]
  83. Suzuki MM, Bird A. 83.  2008. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 9:465–76 [Google Scholar]
  84. Eckhardt F, Lewin J, Cortese R. 84.  et al. 2006. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat. Genet. 38:1378–85 [Google Scholar]
  85. Weber M, Hellmann I, Stadler MB. 85.  et al. 2007. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat. Genet. 39:457–66 [Google Scholar]
  86. Illingworth R, Kerr A, Desousa D. 86.  et al. 2008. A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 6:e22 [Google Scholar]
  87. Rakyan VK, Down TA, Thorne NP. 87.  et al. 2008. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res. 18:1518–29 [Google Scholar]
  88. Chim SS, Tong YK, Chiu RW. 88.  et al. 2005. Detection of the placental epigenetic signature of the maspin gene in maternal plasma. PNAS 102:14753–58 [Google Scholar]
  89. Chan KC, Ding C, Gerovassili A. 89.  et al. 2006. Hypermethylated RASSF1A in maternal plasma: a universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin. Chem. 52:2211–18 [Google Scholar]
  90. Tong YK, Ding C, Chiu RW. 90.  et al. 2006. Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: theoretical and empirical considerations. Clin. Chem. 52:2194–202 [Google Scholar]
  91. Tong YK, Chiu RW, Akolekar R. 91.  et al. 2010. Epigenetic-genetic chromosome dosage approach for fetal trisomy 21 detection using an autosomal genetic reference marker. PLoS ONE 5:e15244 [Google Scholar]
  92. Tong YK, Jin S, Chiu RW. 92.  et al. 2010. Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clin. Chem. 56:90–98 [Google Scholar]
  93. Tsui DW, Lam YM, Lee WS. 93.  et al. 2010. Systematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards syndrome. PLoS ONE 5:e15069 [Google Scholar]
  94. Papageorgiou EA, Karagrigoriou A, Tsaliki E. 94.  et al. 2011. Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat. Med. 17:510–13 [Google Scholar]
  95. Yuen RK, Peñaherrera MS, von Dadelszen P. 95.  et al. 2010. DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur. J. Hum. Genet. 18:1006–12 [Google Scholar]
  96. Blair JD, Yuen RK, Lim BK. 96.  et al. 2013. Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Mol. Hum. Reprod. 19:697–708 [Google Scholar]
  97. Chu T, Bunce K, Shaw P. 97.  et al. 2014. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta. PLoS ONE 9:e107318 [Google Scholar]
  98. Poon LL, Leung TN, Lau TK, Lo YM. 98.  2000. Presence of fetal RNA in maternal plasma. Clin. Chem. 46:1832–34 [Google Scholar]
  99. Pang WW, Tsui MH, Sahota D. 99.  et al. 2009. A strategy for identifying circulating placental RNA markers for fetal growth assessment. Prenat. Diagn. 29:495–504 [Google Scholar]
  100. Ng EK, Leung TN, Tsui NB. 100.  et al. 2003. The concentration of circulating corticotropin-releasing hormone mRNA in maternal plasma is increased in preeclampsia. Clin. Chem. 49:727–31 [Google Scholar]
  101. Lo YM, Tsui NB, Chiu RW. 101.  et al. 2007. Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat. Med. 13:218–23 [Google Scholar]
  102. Tsui NB, Wong BC, Leung TY. 102.  et al. 2009. Non-invasive prenatal detection of fetal trisomy 18 by RNA-SNP allelic ratio analysis using maternal plasma SERPINB2 mRNA: a feasibility study. Prenat. Diagn. 29:1031–37 [Google Scholar]
  103. Tsui NB, Jiang P, Wong YF. 103.  et al. 2014. Maternal plasma RNA sequencing for genome-wide transcriptomic profiling and identification of pregnancy-associated transcripts. Clin. Chem. 60:954–62 [Google Scholar]
  104. Koh W, Pan W, Gawad C. 104.  et al. 2014. Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. PNAS 111:7361–66 [Google Scholar]
  105. Hahn S, Rusterholz C, Hösli I, Lapaire O. 105.  2011. Cell-free nucleic acids as potential markers for preeclampsia. Placenta 32:Suppl.S17–20 [Google Scholar]
  106. Oudejans CBM. 106.  2015. Maternal plasma RNA sequencing. Clin. Biochem. 48942–47
/content/journals/10.1146/annurev-med-091014-115715
Loading
/content/journals/10.1146/annurev-med-091014-115715
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error