Liquid biopsies: DNA methylation analyses in circulating cell-free DNA

Hu Zeng^{a, #},
Bo He^{b, #},
Chengqi Yi^{a, b, c
, ,},
Jinying Peng^{a
, ,}

a.
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China
b.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
c.
Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

More Information

Corresponding author: E-mail address: chengqi.yi@pku.edu.cn (Chengqi Yi); E-mail address: jypengpku@pku.edu.cn (Jinying Peng)

These authors contributed equally to this work.

摘要

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Abstract: Analysis of patient's materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA (cfDNA) is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This review summarizes the various investigational applications of cfDNA methylation and its oxidized derivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring. The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.
- Circulating cell-free DNA /
- DNA methylation /
- Cancer detection /
- Biomarkers /
- Methylation analysis methods
These authors contributed equally to this work.
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参考文献(113)

[1]	Abdel-Wahab, O., Mullally, A., Hedvat, C. et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies Blood, 114 (2009),pp. 144-147
[2]	Allen, E.G., Freeman, S.B., Druschel, C. et al. Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction: a report from the Atlanta and National Down Syndrome Projects Hum. Genet., 125 (2009),pp. 41-52
[3]	Barzilai, N., Huffman, D.M., Muzumdar, R.H. et al. The critical role of metabolic pathways in aging Diabetes, 61 (2012),pp. 1315-1322
[4]	Baylin, S.B., Jones, P.A. A decade of exploring the cancer epigenome - biological and translational implications Nat. Rev. Cancer, 11 (2011),pp. 726-734
[5]	Baylin, S.B., Jones, P.A. Epigenetic determinants of cancer Cold Spring Harb. Perspect. Biol., 8 (2016)
[6]	Bird, A. DNA methylation patterns and epigenetic memory Genes Dev., 16 (2002),pp. 6-21
[7]	Board, R.E., Knight, L., Greystoke, A. et al. DNA methylation in circulating tumour DNA as a biomarker for cancer Biomark. Insights, 2 (2008),pp. 307-319
[8]	Botezatu, I. Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism Clin. Chem., 46 (2000),pp. 1078-1084
[9]	Branco, M.R., Ficz, G., Reik, W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome Nat. Rev. Genet., 13 (2011),pp. 7-13
[10]	Burnham, P., Khush, K., De Vlaminck, I. Myriad applications of circulating cell-free DNA in precision organ transplant monitoring Annal. Am. Thorac. Soc., 14 (2017),pp. S237-S241
[11]	Chan, K.C., Jiang, P., Chan, C.W. et al. Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing Proc. Natl. Acad. Sci. U. S. A., 110 (2013),pp. 18761-18768
[12]	Chan, K.C.A., Leung, S.F., Yeung, S.W. et al. Quantitative analysis of the transrenal excretion of circulating EBV DNA in nasopharyngeal carcinoma patients Clin. Cancer Res., 14 (2008),p. 4809
[13]	Chim, S.S., Jin, S., Lee, T.Y. 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., 54 (2008),pp. 500-511
[14]	Chim, S.S.C., Tong, Y.K., Chiu, R.W.K. et al. Detection of the placental epigenetic signature of the maspin gene in maternal plasma Proc. Natl. Acad. Sci. U. S. A., 102 (2005),pp. 14753-14758
[15]	Cimmino, L., Abdel-Wahab, O., Levine, R.L. et al. TET family proteins and their role in stem cell differentiation and transformation Cell Stem Cell, 9 (2011),pp. 193-204
[16]	Dalton, S.R., Bellacosa, A. DNA demethylation by TDG Epigenomics, 4 (2012),pp. 459-467
[17]	Daly, K.P. Circulating donor-derived cell-free DNA: a true biomarker for cardiac allograft rejection? Ann. Transl. Med., 3 (2015),p. 47
[18]	De Mattos-Arruda, L. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma Nat. Commun., 6 (2015),p. 8839
[19]	De Mattos-Arruda, L., Mayor, R., Ng, C.K. et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma Nat. Commun., 6 (2015),p. 8839
[20]	De Mattos-Arruda, L., Weigelt, B., Cortes, J. et al. Ann. Oncol., 25 (2014),pp. 1729-1735
[21]	De Vlaminck, I. Noninvasive monitoring of infection and rejection after lung transplantation Proc. Natl. Acad. Sci. U. S. A., 112 (2015),pp. 13336-13341
[22]	Delhommeau, F., Dupont, S., Della Valle, V. et al. N. Engl. J. Med., 360 (2009),pp. 2289-2301
[23]	Diehl, F., Schmidt, K., Choti, M.A. et al. Circulating mutant DNA to assess tumor dynamics Nat. Med., 14 (2008),pp. 985-990
[24]	Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps Nat. Rev. Genet., 8 (2007),pp. 286-298
[25]	Feng, S., Jacobsen, S.E., Reik, W. Epigenetic reprogramming in plant and animal development Science, 330 (2010),pp. 622-627
[26]	Fleischhacker, M., Schmidt, B. Circulating nucleic acids (CNAs) and cancer - a survey Biochim. Biophys. Acta, 1775 (2007),pp. 181-232
[27]	Frommer, M., McDonald, L.E., Millar, D.S. et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands Proc. Natl. Acad. Sci. U. S. A., 89 (1992),pp. 1827-1831
[28]	Gadi, V.K., Nelson, J.L., Boespflug, N.D. et al. Soluble donor DNA concentrations in recipient serum correlate with pancreas-kidney rejection Clin. Chem., 52 (2006),pp. 379-382
[29]	Garcia-Olmo, D.C., Dominguez, C., Garcia-Arranz, M. et al. Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells Cancer Res., 70 (2010),pp. 560-567
[30]	Globisch, D., Munzel, M., Muller, M. et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates PLoS One, 5 (2010)
[31]	Gold, B., Cankovic, M., Furtado, L.V. et al. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology J. Mol. Diagn., 17 (2015),pp. 209-224
[32]	Gould, T.J., Lysov, Z., Liaw, P.C. Extracellular DNA and histones: double-edged swords in immunothrombosis J. Thromb. Haemostasis, 13 (2015),pp. S82-S91
[33]	Guibert, J., Benachi, A., Grebille, A.G. et al. Hum. Reprod., 18 (2003),pp. 1733-1736
[34]	Guo, H., Zhu, P., Wu, X. et al. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing Genome Res., 23 (2013),pp. 2126-2135
[35]	Guo, S., Diep, D., Plongthongkum, N. et al. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA Nat. Genet., 49 (2017),pp. 635-642
[36]	Haffner, M.C., Chaux, A., Meeker, A.K. et al. Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers Oncotarget, 2 (2011),pp. 627-637
[37]	Han, D., Lu, X., Shih, A.H. et al. A highly sensitive and robust method for genome-wide 5hmC profiling of rare cell populations Mol. Cell, 63 (2016),pp. 711-719
[38]	He, Y.F., Li, B.Z., Li, Z. et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA Science, 333 (2011),pp. 1303-1307
[39]	Hernndez, H.G., Tse, M.Y., Pang, S.C. et al. Optimizing methodologies for PCR-based DNA methylation analysis Biotechniques, 55 (2013),pp. 181-197
[40]	Hsu, C.H., Peng, K.L., Kang, M.L. et al. TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases Cell Rep., 2 (2012),pp. 568-579
[41]	Irizarry, R.A., Ladd-Acosta, C., Wen, B. et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores Nat. Genet., 41 (2009),pp. 178-186
[42]	Ito, S., D'Alessio, A.C., Taranova, O.V. et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification Nature, 466 (2010),pp. 1129-1133
[43]	Jaenisch, R., Bird, A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals Nat. Genet., 33 (2003),pp. 245-254
[44]	Jahr, S. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells Cancer Res., 61 (2001),pp. 1659-1665
[45]	Jamal-Hanjani, M., Wilson, G.A., Horswell, S. et al. Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer Ann. Oncol., 27 (2016),pp. 862-867
[46]	Jin, S.G., Jiang, Y., Qiu, R. et al. Cancer Res., 71 (2011),pp. 7360-7365
[47]	Jones, P.A. Functions of DNA methylation: islands, start sites, gene bodies and beyond Nat. Rev. Genet., 13 (2012),pp. 484-492
[48]	Jung, K., Fleischhacker, M., Rabien, A. Cell-free DNA in the blood as a solid tumor biomarker-a critical appraisal of the literature Clin. Chim. Acta, 411 (2010),pp. 1611-1624
[49]	Kaplan, M.J., Radic, M. Neutrophil extracellular traps: double-edged swords of innate immunity J. Immunol., 189 (2012),pp. 2689-2695
[50]	Kinnings, S.L., Geis, J.A., Almasri, E. et al. Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing Prenat. Diagn., 35 (2015),pp. 816-822
[51]	Konstandin, N., Bultmann, S., Szwagierczak, A. et al. Leukemia, 25 (2011),pp. 1649-1652
[52]	Kraus, T.F., Guibourt, V., Kretzschmar, H.A. 5-Hydroxymethylcytosine, the “Sixth Base”, during brain development and ageing J. Neural Transm. (Vienna), 122 (2015),pp. 1035-1043
[53]	Kriaucionis, S., Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain Science, 324 (2009),pp. 929-930
[54]	Legendre, C., Gooden, G.C., Johnson, K. et al. Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer Clin. Epigenetics, 7 (2015),p. 100
[55]	Lehmann-Werman, R., Neiman, D., Zemmour, H. et al. Identification of tissue-specific cell death using methylation patterns of circulating DNA Proc. Natl. Acad. Sci. U. S. A., 113 (2016),pp. E1826-E1834
[56]	Leon, S.A., Shapiro, B., Sklaroff, D.M. et al. Free DNA in the serum of cancer patients and the effect of therapy Cancer Res., 37 (1977),pp. 646-650
[57]	Li, W., Zhang, X., Lu, X. et al. 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers Cell Res., 27 (2017),pp. 1243-1257
[58]	Lian, C.G., Xu, Y., Ceol, C. et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma Cell, 150 (2012),pp. 1135-1146
[59]	Lissa, D., Robles, A.I. Methylation analyses in liquid biopsy Transl. Lung Cancer Res., 5 (2016),pp. 492-504
[60]	Lister, R., O'Malley, R.C., Tonti-Filippini, J. et al. Cell, 133 (2008),pp. 523-536
[61]	Lister, R., Pelizzola, M., Dowen, R.H. et al. Human DNA methylomes at base resolution show widespread epigenomic differences Nature, 462 (2009),pp. 315-322
[62]	Lo, Y.M. Rapid clearance of fetal DNA from maternal plasma Am. J. Hum. Genet., 64 (1999),pp. 218-224
[63]	Lo, Y.M., Chan, K.C., Sun, H. et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus Sci. Transl. Med., 2 (2010)
[64]	Lo, Y.M.D. Presence of fetal DNA in maternal plasma and serum Lancet, 350 (1997),pp. 485-487
[65]	Lo, Y.M.D. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus Sci. Transl. Med., 2 (2010)
[66]	Lo, Y.M.D., Tein, M.S.C., Pang, C.C.P. et al. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients Lancet, 351 (1998),pp. 1329-1330
[67]	Lui, Y.Y., Woo, K.S., Wang, A.Y. et al. Origin of plasma cell-free DNA after solid organ transplantation Clin. Chem., 49 (2003),pp. 495-496
[68]	Lun, F.M., Chiu, R.W., Sun, K. et al. Noninvasive prenatal methylomic analysis by genomewide bisulfite sequencing of maternal plasma DNA Clin. Chem., 59 (2013),pp. 1583-1594
[69]	Maiti, A., Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites J. Biol. Chem., 286 (2011),pp. 35334-35338
[70]	Mandel, P., Metais, P. Les acides nucléiques du plasma sanguin chez l’homme C. R. Acad. Sci. Paris, 142 (1948),pp. 241-243
[71]	Meissner, A., Mikkelsen, T.S., Gu, H. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells Nature, 454 (2008),pp. 766-770
[72]	Mithani, S.K. Mitochondrial resequencing arrays detect tumor-specific mutations in salivary rinses of patients with head and neck cancer Clin. Cancer Res., 13 (2007),pp. 7335-7340
[73]	Moreira, V.G., Garca, B.P., Martn, J.M.B. et al. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation Clin. Chem., 55 (2009),pp. 1958-1966
[74]	Mouliere, F., El Messaoudi, S., Pang, D. et al. Multi-marker analysis of circulating cell-free DNA toward personalized medicine for colorectal cancer Mol. Oncol., 8 (2014),pp. 927-941
[75]	Mouliere, F., Robert, B., Arnau Peyrotte, E. et al. High fragmentation characterizes tumour-derived circulating DNA PLoS One, 6 (2011)
[76]	Ng, E.K., Tsui, N.B., Lau, T.K. et al. mRNA of placental origin is readily detectable in maternal plasma Proc. Natl. Acad. Sci. U. S. A., 100 (2003),pp. 4748-4753
[77]	Niu, Q., Li, X., Xia, D. et al. MicroRNA-186 affects the proliferation of tumor cells via yes-associated protein 1 in the occurrence and development of pancreatic cancer Exp. Ther. Med., 14 (2017),pp. 2094-2100
[78]	Old, R.W., Crea, F., Puszyk, W. et al. Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome Reprod. Biomed. Online, 15 (2007),pp. 227-235
[79]	Ono, R., Taki, T., Taketani, T. et al. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23) Cancer Res., 62 (2002),pp. 4075-4080
[80]	Ostrow, K.L., Hoque, M.O., Loyo, M. et al. Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR Clin. Cancer Res., 16 (2010),pp. 3463-3472
[81]	Pan, W., Gu, W., Nagpal, S. et al. Brain tumor mutations detected in cerebral spinal fluid Clin. Chem., 61 (2015),pp. 514-522
[82]	Pfaffeneder, T., Hackner, B., Truss, M. et al. The discovery of 5-formylcytosine in embryonic stem cell DNA Angew. Chem. Int. Ed. Engl., 50 (2011),pp. 7008-7012
[83]	Poon, L.L.M., Leung, T.N., Lau, T.K. et al. Differential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma Clin. Chem., 48 (2002),pp. 35-41
[84]	Powrozek, T., Krawczyk, P., Kucharczyk, T. et al. Septin 9 promoter region methylation in free circulating DNA-potential role in noninvasive diagnosis of lung cancer: preliminary report Med. Oncol., 31 (2014),p. 917
[85]	Rodrigues Filho, E.M. Elevated cell-free plasma DNA level as an independent predictor of mortality in patients with severe traumatic brain injury J. Neurotrauma, 31 (2014),pp. 1639-1646
[86]	Schtz, E., Fischer, A., Beck, J. et al. Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: a prospective, observational, multicenter cohort study PLoS Med., 14 (2017)
[87]	Schwarzenbach, H., Hoon, D.S., Pantel, K. Cell-free nucleic acids as biomarkers in cancer patients Nat. Rev. Cancer, 11 (2011),pp. 426-437
[88]	Smith, Z.D., Meissner, A. DNA methylation: roles in mammalian development Nat. Rev. Genet., 14 (2013),pp. 204-220
[89]	Snyder, T.M., Khush, K.K., Valantine, H.A. et al. Universal noninvasive detection of solid organ transplant rejection Proc. Natl. Acad. Sci. U. S. A., 108 (2011),pp. 6229-6234
[90]	Song, C.X., Szulwach, K.E., Fu, Y. et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine Nat. Biotechnol., 29 (2011),pp. 68-72
[91]	Song, C.X., Yin, S., Ma, L. et al. 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages Cell Res., 27 (2017),pp. 1231-1242
[92]	Sriram, K.B., Relan, V., Clarke, B.E. et al. Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas BMC Cancer, 12 (2012),p. 428
[93]	Stroun, M., Anker, P., Maurice, P. et al. Neoplastic characteristics of the DNA found in the plasma of cancer patients Oncology, 46 (1989),pp. 318-322
[94]	Stroun, M., Maurice, P., Vasioukhin, V. et al. The origin and mechanism of circulating DNA Ann. N. Y. Acad. Sci., 906 (2000),pp. 161-168
[95]	Sun, K., Jiang, P., Chan, K.C. et al. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments Proc. Natl. Acad. Sci. U. S. A., 112 (2015),pp. E5503-E5512
[96]	Tahiliani, M., Koh, K.P., Shen, Y. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 Science, 324 (2009),pp. 930-935
[97]	Tanaka, K., Okamoto, A. Degradation of DNA by bisulfite treatment Bioorg. Med. Chem. Lett., 17 (2007),pp. 1912-1915
[98]	Tefferi, A., Lim, K.H., Levine, R. N. Engl. J. Med., 361 (2009),p. 1117
[99]	Thienpont, B., Steinbacher, J., Zhao, H. et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity Nature, 537 (2016),pp. 63-68
[100]	Thierry, A.R. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts Nucleic Acids Res., 38 (2010),pp. 6159-6175
[101]	To, E.W.H. Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma Clin. Cancer Res., 9 (2003),pp. 3254-3259
[102]	Tong, Y.K., Ding, C., Chiu, R.W. et al. Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: theoretical and empirical considerations Clin. Chem., 52 (2006),pp. 2194-2202
[103]	Trejo-Becerril, C., Perez-Cardenas, E., Taja-Chayeb, L. et al. PLoS One, 7 (2012)
[104]	Wan, J.C.M., Massie, C., Garcia-Corbacho, J. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA Nat. Rev. Cancer, 17 (2017),pp. 223-238
[105]	Wang, E., Batey, A., Struble, C. et al. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma Prenat. Diagn., 33 (2013),pp. 662-666
[106]	Wang, Y. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord Proc. Natl. Acad. Sci. U. S. A., 112 (2015),pp. 9704-9709
[107]	Wang, Y., Chen, M., Xiao, N. et al. Gene, 590 (2016),pp. 142-148
[108]	Wen, L., Li, J., Guo, H. et al. Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients Cell Res., 25 (2015),p. 1376
[109]	Wu, H., D'Alessio, A.C., Ito, S. et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells Genes Dev., 25 (2011),pp. 679-684
[110]	Wu, X., Zhang, Y. TET-mediated active DNA demethylation: mechanism, function and beyond Nat. Rev. Genet., 18 (2017),pp. 517-534
[111]	Xu, R.H., Wei, W., Krawczyk, M. et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma Nat. Mater., 16 (2017),pp. 1155-1161
[112]	Yang, H., Liu, Y., Bai, F. et al. Oncogene, 32 (2013),pp. 663-669
[113]	Zimmermann, B., Hill, M., Gemelos, G. et al. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci Prenat. Diagn., 32 (2012),pp. 1233-1241