Molecular Biology Reports

, Volume 40, Issue 7, pp 4349–4360 | Cite as

DNA methylation: the future of crime scene investigation?

  • Branka GrškovićEmail author
  • Dario Zrnec
  • Sanja Vicković
  • Maja Popović
  • Gordan Mršić


Proper detection and subsequent analysis of biological evidence is crucial for crime scene reconstruction. The number of different criminal acts is increasing rapidly. Therefore, forensic geneticists are constantly on the battlefield, trying hard to find solutions how to solve them. One of the essential defensive lines in the fight against the invasion of crime is relying on DNA methylation. In this review, the role of DNA methylation in body fluid identification and other DNA methylation applications are discussed. Among other applications of DNA methylation, age determination of the donor of biological evidence, analysis of the parent-of-origin specific DNA methylation markers at imprinted loci for parentage testing and personal identification, differentiation between monozygotic twins due to their different DNA methylation patterns, artificial DNA detection and analyses of DNA methylation patterns in the promoter regions of circadian clock genes are the most important ones. Nevertheless, there are still a lot of open chapters in DNA methylation research that need to be closed before its final implementation in routine forensic casework.


Epigenetics DNA methylation Body fluid identification DNA methylation applications Forensic science 


  1. 1.
    Virkler K, Lednev IK (2009) Analysis of body fluids for forensic purposes: from laboratory testing to non-destructive rapid confirmatory identification at a crime scene. Forensic Sci Int 188(1–3):1–17. doi: 10.1016/j.forsciint.2009.02.013 PubMedCrossRefGoogle Scholar
  2. 2.
    Lee HY, Park MJ, Choi A, An JH, Yang WI, Shin KJ (2011) Potential forensic application of DNA methylation profiling to body fluid identification. Int J Legal Med 126(1):55–62. doi: 10.1007/s00414-011-0569-2 PubMedCrossRefGoogle Scholar
  3. 3.
    Frumkin D, Wasserstrom A, Budowle B, Davidson A (2011) DNA methylation-based forensic tissue identification. Forensic Sci Int Genet 5:517–524. doi: 10.1016/j.fsigen.2010.12.001 PubMedCrossRefGoogle Scholar
  4. 4.
    Fleming R, Harbison S (2010) The development of a mRNA multiplex RT-PCR assay for the definitive identification of body fluids. Forensic Sci Int Genet 4:244–256. doi: 10.1016/j.fsigen.2009.10.006 PubMedCrossRefGoogle Scholar
  5. 5.
    Zubakov D, Boersma AWM, Choi Y, van Kuijk PF, Wiemer EAC, Kayser M (2010) MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation. Int J Legal Med 124(3):217–226. doi: 10.1007/s00414-009-0402-3 PubMedCrossRefGoogle Scholar
  6. 6.
    Bibikova M, Fan JB (2010) Genome-wide DNA methylation profiling. WIREs Syst Biol Med 2:210–223. doi: 10.1002/wsbm.35 CrossRefGoogle Scholar
  7. 7.
    Bell JT, Tsai PC, Yang TP et al (2012) Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet 8(4):e1002629. doi: 10.1371/journal.pgen.1002629 PubMedCrossRefGoogle Scholar
  8. 8.
    Zubakov D, Liu F, Choi Y, van Ljcken WFJ, Oostra B, van Duijn CM, Lewin J, Kayser M (2011) mRNA expression and DNA methylation biomarkers for estimating chronological age from blood. In: 24th World Congress of the International Society for Forensic Genetics (ISFG).
  9. 9.
    Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S, Vilain E (2011) Epigenetic predictor of age. PLoS One 6:e14821. doi: 10.1371/journal.pone.0014821 PubMedCrossRefGoogle Scholar
  10. 10.
    Zhao G, Yang Q, Huang D, Yu C, Yang R, Chen H, Mei K (2005) Study on the application of parent-of-origin specific DNA methylation markers to forensic genetics. Forensic Sci Int 154(2–3):122–127. doi: 10.1016/j.forsciint.2004.09.123 PubMedCrossRefGoogle Scholar
  11. 11.
    Nakayashiki N, Takamiya M, Shimamoto K, Aoki Y, Hashiyada M (2009) Investigation of the methylation status around parent-of-origin detectable SNPs in imprinted genes. Forensic Sci Int Genet 3(4):227–232PubMedCrossRefGoogle Scholar
  12. 12.
    Coolen MW, Statham AL, Qu W, Campbell MJ, Henders AK, Montgomery GW, Martin NG, Clark SJ (2011) Impact of the genome on the epigenome is manifested in DNA methylation patterns of imprinted regions in monozygotic and dizygotic twins. PLoS One 6(10):e25590. doi: 10.1371/journal.pone.0025590 PubMedCrossRefGoogle Scholar
  13. 13.
    Coolen MW, Statham AL, Gardiner-Garden M, Clark SJ (2007) Genomic profiling of CpG methylation and allelic specificity using quantitative high throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res 35:e119. doi: 10.1093/nar/gkm662 PubMedCrossRefGoogle Scholar
  14. 14.
    Li C, Zhang S, Que T, Li L, Zhao S (2011) Identical but not the same: the value of DNA methylation profiling in forensic discrimination within monozygotic twins. Forensic Sci Int 3(1):e337–e338. doi: 10.1016/j.fsigss.2011.09.031 Google Scholar
  15. 15.
    Frumkin D, Wasserstrom A, Davidson A, Grafit A (2010) Authentication of forensic DNA samples. Forensic Sci Int Genet 4:95–103. doi: 10.1016/j.fsigen.2009.06.009 PubMedCrossRefGoogle Scholar
  16. 16.
    Nakatome M, Orii M, Hamajima M, Hirata Y, Uemura M, Hirayama S, Isobe I (2011) Methylation analysis of circadian clock gene promoters in forensic autopsy specimens. Leg Med (Tokyo) 13(4):205–209. doi: 10.1016/j.legalmed.2011.03.001 CrossRefGoogle Scholar
  17. 17.
    Henikoff S, Matzke MA (1997) Exploring and explaining epigenetic effects. Trends Genet 13:293–295. doi: 10.1016/S0168-9525(97)01219-5 PubMedCrossRefGoogle Scholar
  18. 18.
    Russo VEA, Martienssen RA, Riggs AD (1996) Epigenetic mechanisms of gene regulation. Cold Spring Harbor, New YorkGoogle Scholar
  19. 19.
    Gibney ER, Nolan CM (2010) Epigenetics and gene expression. Heredity 105(1):4–13PubMedCrossRefGoogle Scholar
  20. 20.
    Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8:253–262. doi: 10.1038/nrg2045 PubMedCrossRefGoogle Scholar
  21. 21.
    Hamilton JP (2011) Epigenetics: principles and practice. Dig Dis 29:130–135. doi: 10.1159/000323874 PubMedCrossRefGoogle Scholar
  22. 22.
    Bird A, Macleod D (2004) Reading the DNA methylation signal. Cold Spring Harb Symp Quant Biol 69:113–118. doi: 10.1101/sqb.2004.69.113 PubMedCrossRefGoogle Scholar
  23. 23.
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080. doi: 10.1126/science.1063127 PubMedCrossRefGoogle Scholar
  24. 24.
    Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054PubMedCrossRefGoogle Scholar
  25. 25.
    Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232PubMedCrossRefGoogle Scholar
  26. 26.
    Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14(1):9–25PubMedCrossRefGoogle Scholar
  27. 27.
    El-Maarri O (2003) Methods: DNA methylation. Adv Exp Med Biol 544:197–204PubMedCrossRefGoogle Scholar
  28. 28.
    Burgers WA, Fuks F, Kouzarides T (2002) DNA methyltransferases get connected to chromatin. Trends Genet 18:275–277. doi: 10.1016/S0168-9525(02)02667-7 PubMedCrossRefGoogle Scholar
  29. 29.
    Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 99(6):3740–3745. doi: 10.1073/pnas.052410099 PubMedCrossRefGoogle Scholar
  30. 30.
    Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196(2):261–268. doi: 10.1016/0022-2836(87)90689-9 PubMedCrossRefGoogle Scholar
  31. 31.
    Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921. doi: 10.1038/35057062 PubMedCrossRefGoogle Scholar
  32. 32.
    Venter JC, Adams MD, Myers EW et al (2001) The sequence of the human genome. Science 291(5507):1304–1351. doi: 10.1126/science.1058040 PubMedCrossRefGoogle Scholar
  33. 33.
    Ehrlich M (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues or cells. Nucleic Acids Res 10:2709–2721. doi: 10.1093/nar/10.8.2709
  34. 34.
    Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21. doi: 10.1101/gad.947102 PubMedCrossRefGoogle Scholar
  35. 35.
    Antequera F, Bird A (1993) Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci USA 90:11995–11999PubMedCrossRefGoogle Scholar
  36. 36.
    Bird AP, Wolffe AP (1999) Methylation-induced repression—belts, braces, and chromatin. Cell 99:451–454. doi: 10.1016/S0092-8674(00)81532-9 PubMedCrossRefGoogle Scholar
  37. 37.
    Jaenisch R, Harbers K, Jahner D, Stewart C, Stuhlmann H (1982) DNA methylation, retroviruses, and embryogenesis. J Cell Biochem 20(4):331–336PubMedCrossRefGoogle Scholar
  38. 38.
    Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5:e1000602. doi: 10.1371/journal.pgen.1000602 PubMedCrossRefGoogle Scholar
  39. 39.
    Schilling E, Rehli M (2007) Global, comparative analysis of tissue-specific promoter CpG methylation. Genomics 90(3):314–323. doi: 10.1016/j.ygeno.2007.04.011 PubMedCrossRefGoogle Scholar
  40. 40.
    Kitamura E, Igarashi J, Morohashi A, Hida N, Oinuma T, Nemoto N, Song F, Ghosh S, Held WA, Yoshida-Noro C, Nagase H (2007) Analysis of tissue-specific differentially methylated regions (TDMs) in humans. Genomics 89(3):326–337. doi: 10.1016/j.ygeno.2006.11.006 PubMedCrossRefGoogle Scholar
  41. 41.
    Igarashi J, Muroi S, Kawashima H, Wang X, Shinojima Y, Kitamura E, Oinuma T, Nemoto N, Song F, Ghosh S, Held WA, Nagase H (2008) Quantitative analysis of human tissue-specific differences in methylation. Biochem Biophys Res Commun 376(4):658–664. doi: 10.1016/j.bbrc.2008.09.044 PubMedCrossRefGoogle Scholar
  42. 42.
    Song F, Mahmood S, Ghosh S, Liang P, Smiraglia DJ, Nagase H, Held WA (2009) Tissue specific differentially methylated regions (TDMR): changes in DNA methylation during development. Genomics 93(2):130–139. doi: 10.1016/j.ygeno.2008.09.003 PubMedCrossRefGoogle Scholar
  43. 43.
    Jones PA, Laird PW (1999) Cancer-epigenetics comes of age. Nat Genet 21(2):163–167. doi: 10.1038/5947 PubMedCrossRefGoogle Scholar
  44. 44.
    Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174. doi: 10.1016/S0168-9525(99)01971-X PubMedCrossRefGoogle Scholar
  45. 45.
    Baylin SB, Esteller M, Rountree MR, Backman KE, Schuebel K, Herman JG (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10:687–692. doi: 10.1093/hmg/10.7.687 PubMedCrossRefGoogle Scholar
  46. 46.
    Watanabe Y, Maekawa M (2010) Methylation of DNA in cancer. Adv Clin Chem 52:145–167. doi: 10.1016/S0065-2423(10)52006-7 PubMedCrossRefGoogle Scholar
  47. 47.
    Park YJ, Claus R, Weichenhan D, Plass C (2011) Genome-wide epigenetic modifications in cancer. Prog Drug Res 67:25–49PubMedGoogle Scholar
  48. 48.
    Hochedlinger K, Jaenisch R (2006) Nuclear reprogramming and pluripotency. Nature 441:1061–1067. doi: 10.1038/nature04955 PubMedCrossRefGoogle Scholar
  49. 49.
    Huang K, Fan G (2010) DNA methylation in cell differentiation and reprogramming: an emerging systematic view. Regen Med 5(4):531–544. doi: 10.2217/rme.10.35 PubMedCrossRefGoogle Scholar
  50. 50.
    Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N, Simon I, Yakhini Z, Cedar H (2009) Developmental programming of CpG island methylation profiles in the human genome. Nat Struct Mol Biol 16:564–571. doi: 10.1038/nsmb.1594 PubMedCrossRefGoogle Scholar
  51. 51.
    De Carvalho DD, You JS, Jones PA (2010) DNA methylation and cellular reprogramming. Trends Cell Biol 20:609–617. doi: 10.1016/j.tcb.2010.08.003 Google Scholar
  52. 52.
    Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692. doi: 10.1016/j.cell.2007.01.029 PubMedCrossRefGoogle Scholar
  53. 53.
    Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476. doi: 10.1038/nrg2341 PubMedCrossRefGoogle Scholar
  54. 54.
    Gartler SM, Riggs AD (1983) Mammalian X-chromosome inactivation. Annu Rev Genet 17:155–190PubMedCrossRefGoogle Scholar
  55. 55.
    Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428. doi: 10.1038/nrg816 PubMedGoogle Scholar
  56. 56.
    Miranda BA, Jones PA (2007) DNA methylation: the nuts and bolts of repression. J Cell Physiol 213(2):384–390. doi: 10.1002/JCP PubMedCrossRefGoogle Scholar
  57. 57.
    Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H, Domann FE (2002) Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet 31:175–179. doi: 10.1038/ng886 PubMedCrossRefGoogle Scholar
  58. 58.
    Hattori N, Nishino K, Ko YG, Ohgane J, Tanaka S, Shiota K (2004) Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells. J Biol Chem 279:17063–17069. doi: 10.1074/jbc.M309002200 PubMedCrossRefGoogle Scholar
  59. 59.
    Blelloch R, Wang Z, Meissner A, Pollard S, Smith A, Jaenisch R (2006) Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells 24:2007–2013. doi: 10.1634/stemcells.2006-0050 PubMedCrossRefGoogle Scholar
  60. 60.
    Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92. doi: 10.1038/301089a0 PubMedCrossRefGoogle Scholar
  61. 61.
    Sakai T, Toguchida J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP (1991) Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet 48(5):880–888PubMedGoogle Scholar
  62. 62.
    Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55:4525–4530PubMedGoogle Scholar
  63. 63.
    Muller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E, Marth C, Widschwendter M (2003) DNA methylation in serum of breast cancer patients. Cancer Res 63:7641–7645PubMedGoogle Scholar
  64. 64.
    Kim E, Kim Y, Jeong P, Ha Y, Bae S, Kim W (2008) Methylation of the RUNX3 promoter as a potential prognostic marker for bladder tumor. J Urol 180(3):1141–1145. doi: 10.1016/j.juro.2008.05.002 PubMedCrossRefGoogle Scholar
  65. 65.
    Schneider E, Pliushch G, El Hajj N, Galetzka D, Puhl A, Schorsch M, Frauenknecht K, Riepert T, Tresch A, Müller AM, Coerdt W, Zechner U, Haaf T (2010) Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns. Nucleic Acids Res 38(12):3880–3890. doi: 10.1093/nar/gkq126 PubMedCrossRefGoogle Scholar
  66. 66.
    Zubakov D, Hanekamp E, Kokshoorn M, van Ijcken W, Kayser M (2008) Stable RNA markers for identification of blood and saliva stains revealed from whole genome expression analysis of time-wise degraded samples. Int J Legal Med 122:135–142. doi: 10.1007/s00414-007-0182-6 PubMedCrossRefGoogle Scholar
  67. 67.
    Dilbeck L (2006) Use of bluestar forensic in lieu of luminol at crime scenes. J Forensic Identif 56(5):706–720Google Scholar
  68. 68.
    Mozayani A, Nozigila C (2006) The forensic laboratory handbook: procedures and practice. Humana Press Inc., TotowaCrossRefGoogle Scholar
  69. 69.
    Pang BCM, Cheung BKK (2008) Applicability of two commercially available kits for forensic identification of saliva stains. J Forensic Sci 53(5):1117–1122. doi: 10.1111/j.1556-4029.2008.00814.x PubMedCrossRefGoogle Scholar
  70. 70.
    Simich JP, Morris SL, Klick RL, Rittenhouse-Diakun K (1999) Validation of the use of a commercially available kit for the identification of prostate specific antigen (PSA) in semen stains. J Forensic Sci 44:1229–1231PubMedGoogle Scholar
  71. 71.
    Allery JP, Telmon N, Mieusset R, Blanc A, Rouge D (2001) Cytological detection of spermatozoa: comparison of three staining methods. J Forensic Sci 46:349–351PubMedGoogle Scholar
  72. 72.
    Heintzman ND, Ren B (2007) The gateway to transcription: identifying, characterizing and understanding promoters in the eukaryotic genome. Cell Mol Life Sci 64:386–400. doi: 10.1007/s00018-006-6295-0 PubMedCrossRefGoogle Scholar
  73. 73.
    Visser M, Zubakov D, Ballantyne KN, Kayser M (2011) mRNA-based skin identification for forensic applications. Int J Legal Med 125(2):253–263. doi: 10.1007/s00414-010-0545-2 PubMedCrossRefGoogle Scholar
  74. 74.
    Zubakov D, Kokshooorn M, Kloosterman A, Kayser M (2009) New markers for old stains: stable mRNA markers for blood and saliva identification from up to 16-year-old stains. Int J Legal Med 123:71–74. doi: 10.1007/s00414-008-0249-z PubMedCrossRefGoogle Scholar
  75. 75.
    Vennemann M, Koppelkamm A (2010) mRNA profiling in forensic genetics I: possibilities and limitations. Forensic Sci Int 203(1–3):71–75. doi: 10.1016/j.forsciint.2010.07.006 PubMedCrossRefGoogle Scholar
  76. 76.
    Lindenbergh A, de Pagter M, Ramdayal G, Visser M, Zubakov D, Kayser M, Sijen T (2012) A multiplex (m)RNA-profiling system for the forensic identification of body fluids and contact traces. Forensic Sci Int 6:565–577. doi: 10.1016/j.fsigen.2012.01.009 CrossRefGoogle Scholar
  77. 77.
    Phang TW, Shi CY, Chia JN, Ong CN (1994) Amplification of cDNA via RT-PCR using RNA extracted from post-mortem tissue. J Forensic Sci 39(5):1275–1279PubMedGoogle Scholar
  78. 78.
    Meyer S, Temme C, Wahle E (2004) Messenger RNA turnover in eukaryotes: pathways and enzymes. Crit Rev Biochem Mol Biol 39(4):197–216. doi: 10.1080/10409230490513991 PubMedCrossRefGoogle Scholar
  79. 79.
    Brewer G (2002) Messenger RNA decays during aging and development. Age Res Rev 1:607–625. doi: 10.1016/S1568-1637(02)00023-5 CrossRefGoogle Scholar
  80. 80.
    Hanson EK, Lubenow H, Ballantyne J (2009) Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal Biochem 387:303–314. doi: 10.1016/j.ab.2009.01.037 PubMedCrossRefGoogle Scholar
  81. 81.
    Wang Z, Luo H, Pan X, Liao M, Hou Y (2011) A model for data analysis of microRNA expression in forensic body fluid identification. Forensic Sci Int Genet 6(3):419–423. doi: 10.1016/j.fsigen.2011.08.008 PubMedCrossRefGoogle Scholar
  82. 82.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006. doi: 10.1038/cr.2008.282 PubMedCrossRefGoogle Scholar
  83. 83.
    Rossi J (2005) Mammalian Dicer finds a partner. EMBO Rep 6(10):927–929. doi: 10.1038/sj.embor.7400531 PubMedCrossRefGoogle Scholar
  84. 84.
    Bail S, Swerdel M, Liu H, Jiao X, Goff LA, Hart RP, Kiledjian M (2010) Differential regulation of microRNA stability. RNA 16:1032–1039. doi: 10.1261/rna.1851510 PubMedCrossRefGoogle Scholar
  85. 85.
    Chang S, Wen S, Chen D, Jin P (2009) Small regulatory RNAs in neurodevelopmental disorders. Hum Mol Genet 18(R1):R18–R26. doi: 10.1093/hmg/ddp072 PubMedCrossRefGoogle Scholar
  86. 86.
    Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934. doi: 10.1126/science.1149460 PubMedCrossRefGoogle Scholar
  87. 87.
    Sato F, Tsuchiya S, Terasawa K, Tsujimoto G (2009) Intra-platform repeatability and inter-platform comparability of microRNA microarray technology. PLoS One 5:e5540. doi: 10.1371/journal.pone.0005540 CrossRefGoogle Scholar
  88. 88.
    Laird PW (2010) Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet 11(3):191–203. doi: 10.1038/nrg2732 PubMedCrossRefGoogle Scholar
  89. 89.
    Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E, Pikarski E, Young RA, Niveleau A, Cedar H, Simon I (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 38:149–153. doi: 10.1038/ng1719 PubMedCrossRefGoogle Scholar
  90. 90.
    Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Graf S, Tomazou EM, Backdahl L, Johnson N, Herberth M, Howe KL, Jackson DK, Miretti MM, Fiegler H, Marioni JC, Birney E, Hubbard TJ, Carter NP, Tavare S, Beck S (2008) An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 18:1518–1529PubMedCrossRefGoogle Scholar
  91. 91.
    Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schübeler D (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37:853–862. doi: 10.1038/ng1598 PubMedCrossRefGoogle Scholar
  92. 92.
    Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39:457–466. doi: 10.1038/ng1990 PubMedCrossRefGoogle Scholar
  93. 93.
    Illingworth R, Kerr A, Desousa D, Jorgensen H, Ellis P, Stalker J, Jackson D, Clee C, Plumb R, Rogers J, Humphray S, Cox T, Langford C, Bird A (2008) A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol 6:e22. doi: 10.1371/journal.pbio.0060022 PubMedCrossRefGoogle Scholar
  94. 94.
    Rauch T, Pfeifer GP (2005) Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer. Lab Invest 85(9):1172–1180. doi: 10.1038/labinvest.3700311 PubMedCrossRefGoogle Scholar
  95. 95.
    Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69(6):905–914. doi: 10.1016/0092-8674(92)90610-O PubMedCrossRefGoogle Scholar
  96. 96.
    Nan X, Meehan RR, Bird A (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21(21):4886–4892PubMedCrossRefGoogle Scholar
  97. 97.
    Mill J, Petronis A (2009) Profiling DNA methylation from small amounts of genomic DNA starting material: efficient sodium bisulfite conversion and subsequent whole-genome amplification methods. Mol Biol 507:371–381. doi: 10.1007/978-1-59745-522-027 Google Scholar
  98. 98.
    Clark S, Harrison J, Paul CL, Frommer M (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Res 22:2990–2997PubMedCrossRefGoogle Scholar
  99. 99.
    Frommer M, McDonald L, Millar D, Collis C, Watt F, Grigg G, Molloy P, Paul C (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 89:1827–1831PubMedCrossRefGoogle Scholar
  100. 100.
    Grunau C, Clark SJ, Rosenthal A (2001) Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res 29:e65. doi: 10.1093/nar/29.13.e65 PubMedCrossRefGoogle Scholar
  101. 101.
    Genereux DP, Johnson WC, Burden AF, Stoger R, Laird CD (2008) Errors in the bisulfite conversion of DNA: modulating inappropriate and failed conversion frequencies. Nucleic Acids Res 36:e150. doi: 10.1093/nar/gkn691 PubMedCrossRefGoogle Scholar
  102. 102.
    Xu H, Zhao Y, Liu Z, Zhu W, Zhou Y, Zhao Z (2011) Bisulfite genomic sequencing of DNA from dried blood spot microvolume samples. Forensic Sci Int Genet 6(3):306–309. doi: 10.1016/j.fsigen.2011.06.007 PubMedCrossRefGoogle Scholar
  103. 103.
    Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, Burton J, Cox TV, Davies R, Down TA, Haefliger C, Horton R, Howe K, Jackson DK, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R, Seemann S, Thompson C, West T, Rogers J, Olek A, Berlin K, Beck S (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38:1378–1385. doi: 10.1038/ng1909 PubMedCrossRefGoogle Scholar
  104. 104.
    Zhang Y, Jeltsch A (2010) The application of next generation sequencing in DNA methylation analysis. Genes 1(1):85–101. doi: 10.3390/genes1010085 CrossRefGoogle Scholar
  105. 105.
    An JH, Choi A, Shin KJ, Yang WI, Lee HY (2013) DNA methylation-specific multiplex assays for body fluid identification. Int J Legal Med 127(1):35–43. doi: 10.1007/s00414-012-0719-1 PubMedCrossRefGoogle Scholar
  106. 106.
    Madi T, Balamurugan K, Bombardi R, Duncan G, McCord B (2012) The determination of tissue-specific DNA methylation patterns in forensic biofluids using bisulfate modification and pyrosequencing. Electrophoresis 33:1736–1745. doi: 10.1002/elps.201100711 PubMedCrossRefGoogle Scholar
  107. 107.
    Wasserstrom A, Frumkin D, Davidson A, Shpitzen M, Herman Y, Gafny R (2013) Demonstration of DSI-semen—a novel DNA methylation-based forensic semen identification assay. Forensic Sci Int Genet 7(1):136–142. doi: 10.1016/j.fsigen.2012.08.009 PubMedCrossRefGoogle Scholar
  108. 108.
    Naito E, Dewa K, Fukuda M, Sumi H, Wakabayashi Y, Umetsu K, Yuasa I, Yamanouchi H (2003) Novel paternity testing by distinguishing parental alleles at a VNTR locus in the differentially methylated region upstream of the human H19 gene. J Forensic 48(6):1275–1279Google Scholar
  109. 109.
    Xu HD, Naito E, Dewa K, Fukuda M, Sumi H, Yuasa I, Yamanouchi H (2006) Parentally imprinted allele typing at a short tandem repeat locus in intron 1a of imprinted gene KCNQ1. Leg Med (Tokyo) 8(3):139–143CrossRefGoogle Scholar
  110. 110.
    Huang D, Lin X, Chen H, Yang Q, Jie Y, Zhai X, Yin H (2008) Parentally imprinted allele (PIA) typing in the differentially methylated region upstream of the human H19 gene. Forensic Sci Int Genet 2(4):286–291. doi: 10.1016/j.fsigen.2008.03.008 PubMedCrossRefGoogle Scholar
  111. 111.
    Koch CM, Wagner W (2011) Epigenetic-aging-signature to determine age in different tissues. Aging (Albany NY) 3(10):1–10Google Scholar
  112. 112.
    Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102(30):10604–10609. doi: 10.1073/pnas.0500398102 PubMedCrossRefGoogle Scholar
  113. 113.
    Zheng YM, Wang N, Lei LI, Fan JIN (2011) Whole genome amplification in preimplantation genetic diagnosis. J Zhejiang Univ Sci B 12(1):1–11. doi: 10.1631/jzus.B1000196 PubMedCrossRefGoogle Scholar
  114. 114.
    Liu H-C, Hu C-J, Tang Y-C, Chang J-G (2008) A pilot study for circadian gene disturbance in dementia patients. Neurosci Lett 435:229–233. doi: 10.1016/j.neulet.2008.02.041 PubMedCrossRefGoogle Scholar
  115. 115.
    Ordovás JM, Smith CE (2010) Epigenetics and cardiovascular disease. Nat Rev Cardiol 7:510–519. doi: 10.1038/nrcardio.2010.104 PubMedCrossRefGoogle Scholar
  116. 116.
    Taniguchi H, Fernándes AF, Setién F, Ropero S, Ballestar E, Villanueva A, Yamamoto H, Imai K, Shinomura Y, Esteller M (2009) Epigenetic inactivation of the circadian clock gene BMAL1 in hematologic malignancies. Cancer Res 69:8447–8454. doi: 10.1158/0008-5472.CAN-09-0551 PubMedCrossRefGoogle Scholar
  117. 117.
    Kim HC, Kim JC, Roh SA, Yu CS, Yook JH, Oh ST, Kim BS, Park KC, Chang R (2005) Aberrant CpG island methylation in early-onset sporadic gastric carcinoma. J Cancer Res Clin Oncol 131:733–740. doi: 10.1007/s00432-005-0017-0 PubMedCrossRefGoogle Scholar
  118. 118.
    Kuo SJ, Chen ST, Yeh KT, Hou MF, Chang YS, Hsu NC, Chang JG (2009) Disturbance of circadian gene expression in breast cancer. Virchows Arch 454:467–474. doi: 10.1007/s00428-009-0761-7 PubMedCrossRefGoogle Scholar
  119. 119.
    Chen ST, Choo KB, Hou MF, Yeh KT, Kuo SJ, Chang JG (2005) Deregulated expression of the PER1, PER2, and PER3 genes in breast cancers. Carcinogenesis 26:1241–1246. doi: 10.1093/carcin/bgi075 PubMedCrossRefGoogle Scholar
  120. 120.
    Lin YM, Chang JH, Yeh KT, Yang MY, Liu TC, Lin SF, Su WW, Chang JG (2008) Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog 47:925–933. doi: 10.1002/mc.20446 PubMedCrossRefGoogle Scholar
  121. 121.
    An JH, Shin KJ, Yang WI, Lee HY (2012) Body fluid identification in forensics. BMB Rep 45(10):545–553. doi: 10.5483/BMBRep.2012.45.10.206 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Branka Gršković
    • 1
    • 2
    Email author
  • Dario Zrnec
    • 3
  • Sanja Vicković
    • 4
  • Maja Popović
    • 2
    • 5
  • Gordan Mršić
    • 1
    • 2
  1. 1.Forensic Science Centre “Ivan Vučetić”, General Police DirectorateMinistry of InteriorZagrebCroatia
  2. 2.University Center for Forensic SciencesUniversity of SplitSplitCroatia
  3. 3.Faculty of Food Technology and BiotechnologyUniversity of ZagrebZagrebCroatia
  4. 4.Division of Gene Technology, School of BiotechnologyRoyal Institute of Technology, Science for Life LaboratorySolnaSweden
  5. 5.Department of Biology, Faculty of Veterinary MedicineUniversity of ZagrebZagrebCroatia

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