اسیدهای نوکلئیک جنینی در خون مادر برای تشخیص غیر تهاجمی پیش از تولد

مصلایی, میثم; صالحی, رسول

اسیدهای نوکلئیک جنینی در خون مادر برای تشخیص غیر تهاجمی پیش از تولد

نوع مقاله : مقاله مروری

نویسندگان

¹ دانشجوی کارشناسی ارشد، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی و کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

² دانشیار، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

کنیک‌های تهاجمی تشخیص پیش از تولد مثل Chorionic villus sampling (CVS) و آمنیوسنتز دارای هزینه‌ی بالا و خطراتی برای جنین و مادر می‌باشند. مطالعات نشان داده است که اسیدهای نوکلئیک آزاد جنینی در گردش خون مادر وجود دارند. بنا بر این، آزمایش‌ها در سرتاسر دنیا به سمت تشخیص غیر تهاجمی پیش از تولد رفته و نشان داده شده است که این روش‌ها، در مقایسه با روش‌های تشخیص تهاجمی، برتری قابل توجهی از نظر اقتصادی و پزشکی دارد. نکته‌ی مهم در استفاده از اسیدهای نوکلئیک جنینی برای تشخیص پیش از تولد کیفیت قطعات DNA و Messenger RNA (mRNA) به همراه حضور اسیدهای نوکلئیک مادری می‌باشد. آنالیزهای معمول اسیدهای نوکلئیک جنینی، با استفاده از نشانگرهای اختصاصی جنینی در mRNA و DNA انجام می‌شود. این نشانگرهای اختصاصی جنینی شامل تفاوت‌های اپی‌ژنتیک موجود در سلول‌های جنین و مادری است که می‌توان از آن به عنوان نشانگر اختصاصی جنینی استفاده نمود. منبع دیگری که می‌توان آن را به عنوان نشانگر زیستی اختصاصی جنین استفاده نمود، mRNA اختصاصی جنینی می‌باشد. در این زمینه می‌توان از تکنیک‌هایی نظیر Bisulfite sequencing، Digital PCR (Digital polymerase chain reaction) و RT-MLPA (Reverse transcriptase-multiplex ligation-dependent probe amplification) استفاده نمود.

کلیدواژه‌ها

عنوان مقاله [English]

Fetal Nucleic Acids in Maternal Circulation for Noninvasive Prenatal Diagnosis

نویسندگان [English]

Meysam Mosallayi ¹
Rasoul Salehi ²

¹ MSc Student, Pediatric Inherited Diseases Research Center AND Department of Genetics and Molecular Biology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

² Associate Professor, Pediatric Inherited Diseases Research Center AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

چکیده [English]

Invasive techniques of prenatal diagnosis such as amniocentesis and chorionic villus sampling (CVS) are expensive and associated with risks to the mother and the fetus. Studies show that cell-free nucleic acids circulate freely in maternal blood. Therefore, the experiments performed worldwide towards noninvasive prenatal diagnosis (NIPD) have demonstrated great economical and medical benefits compared to the currently used invasive prenatal diagnostic techniques. The important point of using cell-free nucleic acids in maternal plasma for prenatal diagnosis is quality of the recovered DNA and messenger RNA (mRNA) fragments in conjunction with presence of maternal nucleic acids. The current analysis of fetal nucleic acids in maternal plasma is done via using fetal speciﬁc DNA and mRNA markers. Using the fetal-specific markers includes epigenetic differences between the placenta and maternal blood cells that could be used as a fetal-specific marker and also fetal-speciﬁc mRNA in maternal plasma that provides another source of fetal speciﬁc biomarkers. Techniques such as bisulfite sequencing, digital polymerase chain reaction (Digital PCR) and reverse transcriptase-multiplex ligation-dependent probe amplification (RT-MLPA) are used in these cases, too.

کلیدواژه‌ها [English]

Noninvasive diagnosis
Cell-free fetal DNA
Maternal plasma
Aneuploidy

مراجع

Dey M, Sharma S, Aggarwal S. Prenatal screening methods for aneuploidies. N Am J Med Sci 2013; 5(3): 182-90.
Kuliev AM, Modell B, Jackson L, Simpson JL, Brambati B, Rhoads G, et al. Risk evaluation of CVS. Prenat Diagn 1993; 13(3): 197-209.
Bianchi DW. Circulating fetal DNA: its origin and diagnostic potential-a review. Placenta 2004; 25(Suppl A): S93-S101.
Purwosunu Y, Sekizawa A, Koide K, Okazaki S, Farina A, Okai T. Clinical potential for noninvasive prenatal diagnosis through detection of fetal cells in maternal blood. Taiwan J Obstet Gynecol 2006; 45(1): 10-20.
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(9076): 485-7.
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(4): 768-75.
Smid M, Lagona F, de Benassuti L, Ferrari A, Ferrari M, Cremonesi L. Evaluation of different approaches for fetal DNA analysis from maternal plasma and nucleated blood cells. Clin Chem 1999; 45(9): 1570-2.
Houfflin-Debarge V, O'Donnell H, Overton T, Bennett PR, Fisk NM. High sensitivity of fetal DNA in plasma compared to serum and nucleated cells using unnested PCR in maternal blood. Fetal Diagn Ther 2000; 15(2): 102-7.
Alberry M, Maddocks D, Jones M, Abdel HM, 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(5): 415-8.
Wataganara T, Metzenbauer M, Peter I, Johnson KL, Bianchi DW. Placental volume, as measured by 3-dimensional sonography and levels of maternal plasma cell-free fetal DNA. Am J Obstet Gynecol 2005; 193(2): 496-500.
Birch L, English CA, O'Donoghue K, Barigye O, Fisk NM, Keer JT. Accurate and robust quantification of circulating fetal and total DNA in maternal plasma from 5 to 41 weeks of gestation. Clin Chem 2005; 51(2): 312-20.
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(1): 218-24.
Samura O, Miharu N, Hyodo M, Honda H, Ohashi Y, Honda N, et al. Cell-free fetal DNA in maternal circulation after amniocentesis. Clin Chem 2003; 49(7): 1193-5.
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(1): 88-92.
Lo YM, Chan KC, Sun H, Chen EZ, Jiang P, Lun FM, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010; 2(61): 61ra91.
Poon LL, Leung TN, Lau TK, Lo YM. Presence of fetal RNA in maternal plasma. Clin Chem 2000; 46(11): 1832-4.
Go AT, van Vugt JM, Oudejans CB. Non-invasive aneuploidy detection using free fetal DNA and RNA in maternal plasma: recent progress and future possibilities. Hum Reprod Update 2011; 17(3): 372-82.
Bianchi DW, Maron JL, Johnson KL. Insights into fetal and neonatal development through analysis of cell-free RNA in body fluids. Early Hum Dev 2010; 86(11): 747-52.
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(9): 1114-9.
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(6): 1002-11.
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(3): 314-9.
Zhong XY, Holzgreve W, Hahn S. Detection of fetal Rhesus D and sex using fetal DNA from maternal plasma by multiplex polymerase chain reaction. BJOG 2000; 107(6): 766-9.
Lo YM. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art. BJOG 2009; 116(2): 152-7.
Colin Y, Cherif-Zahar B, Le Van KC, Raynal V, van Huffel V, Cartron JP. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood 1991; 78(10): 2747-52.
Wright CF, Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Hum Reprod Update 2009; 15(1): 139-51.
Amicucci P, Gennarelli M, Novelli G, Dallapiccola B. Prenatal diagnosis of myotonic dystrophy using fetal DNA obtained from maternal plasma. Clin Chem 2000; 46(2): 301-2.
Tang NL, Leung TN, Zhang J, Lau TK, Lo YM. Detection of fetal-derived paternally inherited X-chromosome polymorphisms in maternal plasma. Clin Chem 1999; 45(11): 2033-5.
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(1): 45-9.
Chen CP, Chern SR, Wang W. Fetal DNA in maternal plasma: the prenatal detection of a paternally inherited fetal aneuploidy. Prenat Diagn 2000; 20(4): 355-7.
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(41): 14753-8.
Tong YK, Ding C, Chiu RW, Gerovassili A, Chim SS, Leung TY, et al. Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: Theoretical and empirical considerations. Clin Chem 2006; 52(12): 2194-202.
Grunau C, Clark SJ, Rosenthal A. Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res 2001; 29(13): E65.
Chim SS, Jin S, Lee TY, Lun FM, Lee WS, Chan LY, et al. Systematic search for placental DNA-methylation markers on chromosome 21: toward a maternal plasma-based epigenetic test for fetal trisomy 21. Clin Chem 2008; 54(3): 500-11.
Old RW, Crea F, Puszyk W, Hulten MA. Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome. Reprod Biomed Online 2007; 15(2): 227-35.
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(1): 90-8.
Brown L, Brown G, Vacek P, Brown S. Aneuploidy detection in mixed DNA samples by methylation-sensitive amplification and microarray analysis. Clin Chem 2010; 56(5): 805-13.
Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC. Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 2011; 17(4): 510-3.
Patsalis PC, Tsaliki E, Koumbaris G, Karagrigoriou A, Velissariou V, Papageorgiou EA. A new non-invasive prenatal diagnosis of Down syndrome through epigenetic markers and real-time qPCR. Expert Opin Biol Ther 2012; 12(Suppl 1): S155-S161.
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(32): 13116-21.
Tsui NB, Wong BC, Leung TY, Lau TK, Chiu RW, Lo YM. Non-invasive prenatal detection of fetal trisomy 18 by RNA-SNP allelic ratio analysis using maternal plasma SERPINB2 mRNA: a feasibility study. Prenat Diagn 2009; 29(11): 1031-7.
Go AT, Visser A, Mulders MA, Twisk JW, Blankenstein MA, van Vugt JM, et al. C21ORF105, A chromosome 21-encoded mRNA, is not a discriminative marker gene for prediction of Down syndrome in maternal plasma. Prenat Diagn 2007; 27(2): 146-9.
Go AT, Visser A, Mulders MA, Blankenstein MA, van Vugt JM, Oudejans CB. 44 single-nucleotide polymorphisms expressed by placental RNA: assessment for use in noninvasive prenatal diagnosis of trisomy 21. Clin Chem 2007; 53(12): 2223-4.
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(2): 218-23.
Chiu RW, Cantor CR, Lo YM. Non-invasive prenatal diagnosis by single molecule counting technologies. Trends Genet 2009; 25(7): 324-31.
Li PQ, Zhang J, Fan JH, Zhang YZ, Hou HY. Development of noninvasive prenatal diagnosis of trisomy 21 by RT-MLPA with a new set of SNP markers. Arch Gynecol Obstet 2014; 289(1): 67-73.
Xu L, Shi R. Noninvasive prenatal diagnosis using next-generation sequencing. Gynecol Obstet Invest 2014; 77(2): 73-7.
Papasavva T, van Ijcken WF, Kockx CE, van den Hout MC, Kountouris P, Kythreotis L, et al. Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to beta-thalassaemia. Eur J Hum Genet 2013; 21(12): 1403-10.