Cell-free Fetal Nucleic Acid Identifier Markers in Maternal Circulation

Ramezanzadeh, Mahboubeh; Khosravi, Sharifeh; Salehi, Rasoul

Cell-free Fetal Nucleic Acid Identifier Markers in Maternal Circulation

Reviewers

Authors

¹ Department of Genetics and Molecular Medicine, School of Medicine, Bushehr University of Medical Sciences, Bushehr 751463341, Iran

² Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81744-176, Iran

Abstract

From the discovery of cell-free fetal (cff)-DNA in 1997 so far, many studies have been performed on various aspects of cff-nucleic acid. It is undoubted that currently, invasive prenatal diagnosis progresses to the noninvasive test. However, there are many problems. One of the most challenging issues in this field is differentiation and detection of the small amount of cff-nucleic acid in maternal plasma. Many markers and methods have been used for this purpose. This review makes an attempt to review and compare the studies in the field. Six identifier markers including Y-specific sequence, polymorphisms, epigenetic difference, DNA size difference, fetal mRNA, and microRNA as well as the advantages and disadvantages of each marker are discussed. This review provides a relatively perfect set on cff-nucleic acid biomarkers in various physiological and pathological status of pregnancy, helping to review and compare the prior obtained results, and improving designation in future studies.

Keywords

References

1.	Tounta G, Kolialexi A, Papantoniou N, Tsangaris GT, Kanavakis E, Mavrou A. Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis. EPMA J 2011;2:163-71.
2.	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.
3.	Alberry M, Maddocks D, Jones M, Abdel Hadi M, Abdel-Fattah S, Avent N, et al. Free fetal DNA in maternal plasma in anembryonic pregnancies: Confirmation that the origin is the trophoblast. Prenat Diagn 2007;27:415-8.
4.	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.
5.	Guibert J, Benachi A, Grebille AG, Ernault P, Zorn JR, Costa JM. Kinetics of SRY gene appearance in maternal serum: Detection by real time PCR in early pregnancy after assisted reproductive technique. Hum Reprod 2003;18:1733-6.
6.	Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet 1999;64:218-24.
7.	Lun FM, Chiu RW, Chan KC, Leung TY, Lau TK, Lo YM. Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin Chem 2008;54:1664-72.
8.	Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: Introduction of a new noninvasive fetal RHD genotyping service. Transfusion 2002;42:1079-85.
9.	Amicucci P, Gennarelli M, Novelli G, Dallapiccola B. Prenatal diagnosis of myotonic dystrophy using fetal DNA obtained from maternal plasma. Clin Chem 2000;46:301-2.
10.	Chiu RW, Lau TK, Cheung PT, Gong ZQ, Leung TN, Lo YM. Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal plasma analysis: A feasibility study. Clin Chem 2002;48:778-80.
11.	Saito H, Sekizawa A, Morimoto T, Suzuki M, Yanaihara T. Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. Lancet 2000;356:1170.
12.	Leung TN, Zhang J, Lau TK, Chan LY, Lo YM. Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem 2001;47:137-9.
13.	Sekizawa A, Jimbo M, Saito H, Iwasaki M, Sugito Y, Yukimoto Y, et al. Increased cell-free fetal DNA in plasma of two women with invasive placenta. Clin Chem 2002;48:353-4.
14.	Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, et al. Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem 1999;45:1747-51.
15.	Lim JH, Park SY, Kim SY, Kim do J, Choi JE, Kim MH, et al. Effective detection of fetal sex using circulating fetal DNA in first-trimester maternal plasma. FASEB J 2012;26:250-8.
16.	Devaney SA, Palomaki GE, Scott JA, Bianchi DW. Noninvasive fetal sex determination using cell-free fetal DNA: A systematic review and meta-analysis. JAMA 2011;306:627-36.
17.	Nair SP, Peter S, Pillay VV, Remya UM, Krishnaprasad R, Rajammal B. Detection of Y STR markers of male fetal dna in maternal circulation. Indian J Hum Genet 2007;13:69-72. [PUBMED] [Full text]
18.	Fernández-Martínez FJ, Galindo A, Garcia-Burguillo A, Vargas-Gallego C, Nogués N, Moreno-García M, et al. Noninvasive fetal sex determination in maternal plasma: A prospective feasibility study. Genet Med 2012;14:101-6.
19.	Perlado-Marina S, Bustamante-Aragones A, Horcajada L, Trujillo-Tiebas MJ, Lorda-Sanchez I, Ruiz Ramos M, et al. Overview of five-years of experience performing non-invasive fetal sex assessment in maternal blood. Diagnostics (Basel) 2013;3:283-90.
20.	Tsui DW, Chiu RW, Lo YD. Epigenetic approaches for the detection of fetal DNA in maternal plasma. Chimerism 2010;1:30-5.
21.	Page-Christiaens GC, Bossers B, van der Schoot CE, DE Haas M. Use of bi-allelic insertion/deletion polymorphisms as a positive control for fetal genotyping in maternal blood:First clinical experience. Ann N Y Acad Sci 2006;1075:123-9.
22.	Scheffer PG. Noninvasive fetal genotyping of paternally inherited alleles. Netherlands: Utrecht University; 2012.
23.	Pertl B, Sekizawa A, Samura O, Orescovic I, Rahaim PT, Bianchi DW. Detection of male and female fetal DNA in maternal plasma by multiplex fluorescent polymerase chain reaction amplification of short tandem repeats. Hum Genet 2000;106:45-9.
24.	Samura O, Pertl B, Sohda S, Johnson KL, Sekizawa A, Falco VM, et al. Female fetal cells in maternal blood: Use of DNA polymorphisms to prove origin. Hum Genet 2000;107:28-32.
25.	Chow KC, Chiu RW, Tsui NB, Ding C, Lau TK, Leung TN, et al. Mass spectrometric detection of an SNP panel as an internal positive control for fetal DNA analysis in maternal plasma. Clin Chem 2007;53:141-2.
26.	Daniels G, Finning K, Martin P, Massey E. Noninvasive prenatal diagnosis of fetal blood group phenotypes: Current practice and future prospects. Prenat Diagn 2009;29:101-7.
27.	Callinan PA, Feinberg AP. The emerging science of epigenomics. Hum Mol Genet 2006;15:R95-101.
28.	Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet 1999;21:163-7.
29.	Lo YM, Wong IH, Zhang J, Tein MS, Ng MH, Hjelm NM. Quantitative analysis of aberrant p16 methylation using real-time quantitative methylation-specific polymerase chain reaction. Cancer Res 1999;59:3899-903.
30.	Wong IH, Lo YM, Zhang J, Liew CT, Ng MH, Wong N, et al. Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients. Cancer Res 1999;59:71-3.
31.	Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res 1999;59:67-70.
32.	Poon LL, Leung TN, Lau TK, Chow KC, Lo YM. Differential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma. Clin Chem 2002;48:35-41.
33.	Chim SS, Tong YK, Chiu RW, Lau TK, Leung TN, Chan LY, et al. Detection of the placental epigenetic signature of the maspin gene in maternal plasma. Proc Natl Acad Sci U S A 2005;102:14753-8.
34.	Chiu RW, Chim SS, Wong IH, Wong CS, Lee WS, To KF, et al. Hypermethylation of RASSF1A in human and rhesus placentas. Am J Pathol 2007;170:941-50.
35.	Novakovic B, Rakyan V, Ng HK, Manuelpillai U, Dewi C, Wong NC, et al. Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts. Mol Hum Reprod 2008;14:547-54.
36.	Lui YY, Chik KW, Chiu RW, Ho CY, Lam CW, Lo YM. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem 2002;48:421-7.
37.	Tong YK, Jin S, Chiu RW, Ding C, Chan KC, Leung TY, et al. Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clin Chem 2010;56:90-8.
38.	Chan KC, Ding C, Gerovassili A, Yeung SW, Chiu RW, Leung TN, et al. Hypermethylated RASSF1A in maternal plasma: A universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem 2006;52:2211-8.
39.	White HE, Dent CL, Hall VJ, Crolla JA, Chitty LS. Evaluation of a novel assay for detection of the fetal marker RASSF1A: Facilitating improved diagnostic reliability of noninvasive prenatal diagnosis. PLoS One 2012;7:e45073.
40.	Grunau C, Clark SJ, Rosenthal A. Bisulfite genomic sequencing: Systematic investigation of critical experimental parameters. Nucleic Acids Res 2001;29:E65-5.
41.	Tong YK, Chiu RW, Leung TY, Ding C, Lau TK, Leung TN, et al. Detection of restriction enzyme-digested target DNA by PCR amplification using a stem-loop primer: Application to the detection of hypomethylated fetal DNA in maternal plasma. Clin Chem 2007;53:1906-14.
42.	Chan KC, Zhang J, Hui AB, Wong N, Lau TK, Leung TN, et al. Size distributions of maternal and fetal DNA in maternal plasma. Clin Chem 2004;50:88-92.
43.	Li Y, Zimmermann B, Rusterholz C, Kang A, Holzgreve W, Hahn S. Size separation of circulatory DNA in maternal plasma permits ready detection of fetal DNA polymorphisms. Clin Chem 2004;50:1002-11.
44.	Jorgez CJ, Bischoff FZ. Improving enrichment of circulating fetal DNA for genetic testing: Size fractionation followed by whole gene amplification. Fetal Diagn Ther 2009;25:314-9.
45.	Li Y, Di Naro E, Vitucci A, Zimmermann B, Holzgreve W, Hahn S. Detection of paternally inherited fetal point mutations for beta-thalassemia using size-fractionated cell-free DNA in maternal plasma. JAMA 2005;293:843-9.
46.	Ramezanzadeh M, Salehi M, Farajzadegan Z, Kamali S, Salehi R. Detection of paternally inherited fetal point mutations for β-thalassemia in maternal plasma using simple fetal DNA enrichment protocol with or without whole genome amplification: An accuracy assessment. J Matern Fetal Neonatal Med, DOI: 10.3109/14767058.2015.1095883
47.	Dhallan R, Au WC, Mattagajasingh S, Emche S, Bayliss P, Damewood M, et al. Methods to increase the percentage of free fetal DNA recovered from the maternal circulation. JAMA 2004;291:1114-9.
48.	Tungwiwat W, Fucharoen G, Fucharoen S, Ratanasiri T, Sanchaisuriya K, Sae-Ung N. Application of maternal plasma DNA analysis for noninvasive prenatal diagnosis of Hb E-beta-thalassemia. Transl Res 2007;150:319-25.
49.	Liao GJ, Lun FM, Zheng YW, Chan KC, Leung TY, Lau TK, et al. Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin Chem 2011;57:92-101.
50.	Lun FM, Tsui NB, Chan KC, Leung TY, Lau TK, Charoenkwan P, et al. Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. Proc Natl Acad Sci U S A 2008;105:19920-5.
51.	Ding C, Chiu RW, Lau TK, Leung TN, Chan LC, Chan AY, et al. MS analysis of single-nucleotide differences in circulating nucleic acids: Application to noninvasive prenatal diagnosis. Proc Natl Acad Sci U S A 2004;101:10762-7.
52.	Chinnapapagari SK, Holzgreve W, Lapaire O, Zimmermann B, Hahn S. Treatment of maternal blood samples with formaldehyde does not alter the proportion of circulatory fetal nucleic acids (DNA and mRNA) in maternal plasma. Clin Chem 2005;51:652-5.
53.	Poon LL, Leung TN, Lau TK, Lo YM. Presence of fetal RNA in maternal plasma. Clin Chem 2000;46:1832-4.
54.	Ng EK, Tsui NB, Lau TK, Leung TN, Chiu RW, Panesar NS, et al. mRNA of placental origin is readily detectable in maternal plasma. Proc Natl Acad Sci U S A 2003;100:4748-53.
55.	Miura K, Yoshiura K, Miura S, Yamasaki K, Nakayama D, Ishimaru T, et al. Cell-free DNA is more sensitive than cell-free mRNA as a marker for evaluation of fetal-maternal hemorrhage. Clin Chem 2006;52:2121-3.
56.	Ng EK, Leung TN, Tsui NB, Lau TK, Panesar NS, Chiu RW, et al. The concentration of circulating corticotropin-releasing hormone mRNA in maternal plasma is increased in preeclampsia. Clin Chem 2003;49:727-31.
57.	Lo YM, Tsui NB, Chiu RW, Lau TK, Leung TN, Heung MM, et al. Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 2007;13:218-23.
58.	Tsui NB, Chim SS, Chiu RW, Lau TK, Ng EK, Leung TN, et al. Systematic micro-array based identification of placental mRNA in maternal plasma: Towards non-invasive prenatal gene expression profiling. J Med Genet 2004;41:461-7.
59.	Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR. Proc Natl Acad Sci U S A 2007;104:9667-72.
60.	Morales Prieto DM, Markert UR. MicroRNAs in pregnancy. J Reprod Immunol 2011;88:106-11.
61.	Fu G, Brkic J, Hayder H, Peng C. MicroRNAs in human placental development and pregnancy complications. Int J Mol Sci 2013;14:5519-44.
62.	Cross JC, Werb Z, Fisher SJ. Implantation and the placenta: Key pieces of the development puzzle. Science 1994;266:1508-18.
63.	Aplin JD. Developmental cell biology of human villous trophoblast: Current research problems. Int J Dev Biol 2010;54:323-9.
64.	Luo L, Ye G, Nadeem L, Fu G, Yang BB, Honarparvar E, et al. MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. J Cell Sci 2012;125(Pt 13):3124-32.
65.	Morales-Prieto DM, Schleussner E, Markert UR. Reduction in miR-141 is induced by leukemia inhibitory factor and inhibits proliferation in choriocarcinoma cell line JEG-3. Am J Reprod Immunol 2011;66 Suppl 1:57-62.
66.	Li P, Guo W, Du L, Zhao J, Wang Y, Liu L, et al. microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells. Clin Sci (Lond) 2013;124:27-40.
67.	Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.
68.	Ouyang Y, Mouillet JF, Coyne CB, Sadovsky Y. Review: Placenta-specific microRNAs in exosomes-good things come in nano-packages. Placenta 2014;35:S69-73.
69.	Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. Clin Biochem 2013;46:953-60.
70.	Li H, Ge Q, Guo L, Lu Z. Maternal plasma miRNAs expression in preeclamptic pregnancies. Biomed Res Int 2013;2013:970265.
71.	Mouillet JF, Chu T, Hubel CA, Nelson DM, Parks WT, Sadovsky Y. The levels of hypoxia-regulated microRNAs in plasma of pregnant women with fetal growth restriction. Placenta 2010;31:781-4.
72.	Ventura W, Koide K, Hori K, Yotsumoto J, Sekizawa A, Saito H, et al. Placental expression of microRNA-17 and -19b is down-regulated in early pregnancy loss. Eur J Obstet Gynecol Reprod Biol 2013;169:28-32.
73.	Tsochandaridis M, Nasca L, Toga C, Levy-Mozziconacci A. Circulating microRNAs as clinical biomarkers in the predictions of pregnancy complications. Biomed Res Int 2015;2015:294954.

Advanced Biomedical Research