Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies

BMC Medical Genomics

Xiuqing Zhang⁴  Jian Wang⁴  Jun Wang⁴  Yingrui Li⁴  Songgang Li⁴  Weimou Zheng⁴  Lijian Zhao⁴  Hui Jiang⁴  Zhengyu Zhang⁴  Zhongming Tian⁴  Hongyun Zhang⁴  Chunlei Zhang⁴  Shengpei Chen⁴  Zhaoling Xuan⁴  Huifei Chen⁴  Lifu Liu⁴  Yihan Li⁴  Xiaoyu Pan⁴  Yuying Yuan⁴  Peipei Li⁴  Qiyun Li²  Hui Guo²  Linhua Lin²  Xianghua Chai⁴  Wei Wang⁴  Huakun Zhang³  Wen Su¹  Baomin Yin¹  Jianhong Xie¹  Yue Su⁵  Shan Dan⁵  Jiansheng Xie³  Yuqiu Zhou¹  Fang Chen⁴  Jinghui Ren²  Fuman Jiang⁴ 

[1] Zhuhai Institute of Medical Genetics, Zhuhai Municipal Maternal and Child Healthcare Hospital, Zhuhai, China;The Center of Prenatal Diagnosis, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong, China;Central for Prenatal Diagnosis, Shenzhen Maternity and Child Healthcare Hospital, Affiliated Southern Medical University, Shenzhen, China;BGI- Shenzhen, Shenzhen, China;Department of Perinatology, Beijing Obstetrics and Gynecology Hospital-Capital University of Medical Sciences, Beijing, China

关键词: Sex chromosomal aneuploidies;    Autosomal aneuploidies;    Massively parallel sequencing;    Noninvasive Fetal Trisomy (NIFTY) test;   

Others  :  1121268
DOI  :  10.1186/1755-8794-5-57

 received in 2011-12-23, accepted in 2012-11-24,  发布年份 2012

【 摘 要 】

Background

Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy.

Methods

We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping.

Results

16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses.

Conclusion

Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

【 授权许可】

   
2012 Jiang et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Driscoll DA, Gross S: Clinical practice. Prenatal screening for aneuploidy. N Engl J Med 2009, 360(24):2556-2562.
• [2]Bouchlariotou S, Tsikouras P, Dimitraki M, Athanasiadis A, Papoulidis I, Maroulis G, Liberis A, Liberis V: Turner’s syndrome and pregnancy: has the 45, X/47, XXX mosaicism a different prognosis? Own clinical experience and literature review. J Matern Fetal Neonatal Med 2011, 24(5):668-672.
• [3]Leggett V, Jacobs P, Nation K, Scerif G, Bishop DV: Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Dev Med Child Neurol 2010, 52(2):119-129.
• [4]Hofherr SE, Wiktor AE, Kipp BR, Dawson DB, Van Dyke DL: Clinical diagnostic testing for the cytogenetic and molecular causes of male infertility: the Mayo Clinic experience. J Assist Reprod Genet 2011, 28(11):1091-1098.
• [5]Rives N, Simeon N, Milazzo JP, Barthelemy C, Mace B: Meiotic segregation of sex chromosomes in mosaic and non-mosaic XYY males: case reports and review of the literature. Int J Androl 2003, 26(4):242-249.
• [6]Park JH, Burns-Cusato M, Dominguez-Salazar E, Riggan A, Shetty S, Arnold AP, Rissman EF: Effects of sex chromosome aneuploidy on male sexual behavior. Genes Brain Behav 2008, 7(6):609-617.
• [7]Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L: A review of trisomy X (47, XXX). Orphanet J Rare Dis 2010, 5:8. BioMed Central Full Text
• [8]Sybert VP, McCauley E: Turner’s syndrome. N Engl J Med 2004, 351(12):1227-1238.
• [9]Mujezinovic F, Alfirevic Z: Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007, 110(3):687-694.
• [10]Pitukkijronnakorn S, Promsonthi P, Panburana P, Udomsubpayakul U, Chittacharoen A: Fetal loss associated with second trimester amniocentesis. Arch Gynecol Obstet 2011, 284(4):793-797.
• [11]Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH: Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod 2008, 23(9):1968-1975.
• [12]Canick J: Prenatal screening for trisomy 21: recent advances and guidelines. Clin Chem Lab Med 2011, 50(6):1003-1008.
• [13]Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet 1997, 350(9076):485-487.
• [14]Simpson JL: Choosing the best prenatal screening protocol. N Engl J Med 2005, 353(19):2068-2070.
• [15]Bischoff FZ, Sinacori MK, Dang DD, Marquez-Do D, Horne C, Lewis DE, Simpson JL: Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis. Hum Reprod Update 2002, 8(6):493-500.
• [16]Illanes S, Denbow M, Kailasam C, Finning K, Soothill PW: Early detection of cell-free fetal DNA in maternal plasma. Early Hum Dev 2007, 83(9):563-566.
• [17]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):218-224.
• [18]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):312-320.
• [19]Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM: Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998, 62(4):768-775.
• [20]Lo YM, Tsui NB, Chiu RW, Lau TK, Leung TN, Heung MM, Gerovassili A, Jin Y, Nicolaides KH, Cantor CR, et al.: Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 2007, 13(2):218-223.
• [21]Tsui NB, Chiu RW, Ding C, El-Sheikhah A, Leung TN, Lau TK, Nicolaides KH, Lo YM: Detection of trisomy 21 by quantitative mass spectrometric analysis of single-nucleotide polymorphisms. Clin Chem 2005, 51(12):2358-2362.
• [22]Tong YK, Ding C, Chiu RW, Gerovassili A, Chim SS, Leung TY, Leung TN, Lau TK, Nicolaides KH, Lo YM: Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: theoretical and empirical considerations. Clin Chem 2006, 52(12):2194-2202.
• [23]Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, Foo CH, Xie B, Tsui NB, Lun FM, et al.: Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008, 105(51):20458-20463.
• [24]Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR: Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008, 105(42):16266-16271.
• [25]Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, et al.: Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011, 204(3):e201-e211. 205
• [26]Chiu RW, Akolekar R, Zheng YW, Leung TY, Sun H, Chan KC, Lun FM, Go AT, Lau ET, To WW, et al.: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011, 342:c7401.
• [27]Chen EZ, Chiu RW, Sun H, Akolekar R, Chan KC, Leung TY, Jiang P, Zheng YW, Lun FM, Chan LY, et al.: Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 2011, 6(7):e21791.
• [28]Fan HC, Quake SR: Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics. PLoS One 2010, 5(5):e10439.
• [29]Lau TK, Chen F, Pan X, Pooh RK, Jiang F, Li Y, Jiang H, Li X, Chen S, Zhang X: Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing. J Matern Fetal Neonatal Med 2011, 25(8):1370-1374.
• [30]Brownstein Z, Friedman LM, Shahin H, Oron-Karni V, Kol N, Rayyan AA, Parzefall T, Lev D, Shalev S, Frydman M, et al.: Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in middle eastern families. Genome Biol 2011, 12(9):R89. BioMed Central Full Text
• [31]Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, Langley RJ, Zhang L, Lee CC, Schilkey FD, et al.: Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 2011, 3(65):65ra64.
• [32]Cheung MS, Down TA, Latorre I, Ahringer J: Systematic bias in high-throughput sequencing data and its correction by BEADS. Nucleic Acids Res 2011, 39(15):e103.
• [33]Aird D, Ross MG, Chen WS, Danielsson M, Fennell T, Russ C, Jaffe DB, Nusbaum C, Gnirke A: Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries. Genome Biol 2011, 12(2):R18. BioMed Central Full Text
• [34]Liao GJ, Lun FM, Zheng YW, Chan KC, Leung TY, Lau TK, Chiu RW, Lo YM: Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin Chem 2011, 57(1):92-101.
• [35]Purwosunu Y, Sekizawa A, Okai T: Detection and quantification of fetal DNA in maternal plasma by using LightCycler technology. Methods Mol Biol 2008, 444:231-238.