Advertisement

Characterization of DNA methylation-based markers for human body fluid identification in forensics: a critical review

  • Farzeen Kader
  • Meenu GhaiEmail author
  • Ademola O. Olaniran
Review

Abstract

Body fluid identification in crime scene investigations aids in reconstruction of crime scenes. Several studies have identified and reported differentially methylated sites (DMSs) and regions (DMRs) which differ between forensically relevant tissues (tDMRs) and body fluids. Diverse factors affect methylation patterns such as the environment, diets, lifestyle, disease, ethnicity, genetic variation, amongst others. Thus, it is important to analyse the stability of markers employed for forensic identification. Furthermore, even though epigenetic modifications are described as stable and heritable, epigenetic inheritance of potential markers for body fluid identification needs to be assessed in the long term. Here, we discuss the current status of reported DNA methylation-based markers and their verification studies. Such thorough investigation is crucial to develop a stable panel of DNA methylation-based markers for accurate body fluid identification.

Keywords

DNA methylation Forensic science Body fluid identification Mutations Genetic variation Heritability 

Notes

Funding information

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

414_2019_2181_MOESM1_ESM.docx (35 kb)
ESM 1 (DOCX 35 kb)

References

  1. 1.
    Nustad HE, Almeida M, Canty AJ, LeBlanc M, Page CM, Melton PE (2018) Epigenetics, heritability and longitudinal analysis. BMC Genet 19(Suppl 1):77.  https://doi.org/10.1186/s12863-018-0648-1 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lalruatfela B (2013) On DNA methylation: An introductory review. Science Vision 13:1-7. ISSN (online):2229-6026.Google Scholar
  3. 3.
    Ghosh S, Yates AJ, Frühwald MC, Miecznikowski JC, Plass C, Smiraglia D (2010) Tissue specific DNA methylation of CpG islands in normal human adult somatic tissues distinguishes neural from non-neural tissues. Epigenetics 5(6):527–538.  https://doi.org/10.4161/epi.5.6.12228 CrossRefGoogle Scholar
  4. 4.
    Pinney SE (2014) Mammalian Non-CpG Methylation: Stem Cells and Beyond. Biology (Basel) 3(4):739–751.  https://doi.org/10.3390/biology3040739 CrossRefGoogle Scholar
  5. 5.
    Yan J, Zierath JR, Barrès R (2011) Evidence for non-CpG methylation in mammals. Exp Cell Res 317(18):2555–2561.  https://doi.org/10.1016/j.yexcr.2011.08.019 CrossRefPubMedGoogle Scholar
  6. 6.
    Kader F, Ghai M (2016) DNA methylation-based variation between human populations. Mol Genet Genomics 292(1):5–35.  https://doi.org/10.1007/s00438-016-1264-2 CrossRefPubMedGoogle Scholar
  7. 7.
    Rienius LE, Acevedo N, Joerink M, Pershagen G, Dahlén SE, Greco D et al (2012) Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One 7(7):e41361.  https://doi.org/10.1371/journal.pone.0041361 CrossRefGoogle Scholar
  8. 8.
    Tammen SA, Friso S, Choi SW (2013) Epigenetics: the link between nature and nurture. Mol Aspects Med 34(4):753–764.  https://doi.org/10.1016/j.mam.2012.07.018 CrossRefPubMedGoogle Scholar
  9. 9.
    Bestor TH, Edwards JR, Boulard M (2015) Notes on the role of dynamic DNA methylation in mammalian development. Proc Natl Acad Sci USA 112(22):6796–6799.  https://doi.org/10.1073/pnas.1415301111 CrossRefPubMedGoogle Scholar
  10. 10.
    Lövkvist C, Dodd IB, Sneppen K, Haerter JO (2016) DNA methylation in human epigenomes depends on local topology of CpG sites. Nucleic Acids Res 44(11):5123–5132.  https://doi.org/10.1093/nar/gkw124 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-Firoozi M, Nouraie M et al (2009) Distinct high-profile methylated genes in colorectal cancer. PLoS One 4:e7012.  https://doi.org/10.1371/journal.pone.0007012 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wiley KL, Treadwell E, Manigaba K, Word B, Lyn-Cook BD (2013) Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus. J Clin Immunol 33(2):342–348.  https://doi.org/10.1007/s10875-012-9803-z CrossRefPubMedGoogle Scholar
  13. 13.
    Chambers JC, Loh M, Lehne B, Drong A, Kriebel J, Motta V, Wahl S, Elliott HR, Rota F, Scott WR, Zhang W, Tan ST, Campanella G, Chadeau-Hyam M, Yengo L, Richmond RC, Adamowicz-Brice M, Afzal U, Bozaoglu K, Mok ZY, Ng HK, Pattou F, Prokisch H, Rozario MA, Tarantini L, Abbott J, Ala-Korpela M, Albetti B, Ammerpohl O, Bertazzi PA, Blancher C, Caiazzo R, Danesh J, Gaunt TR, de Lusignan S, Gieger C, Illig T, Jha S, Jones S, Jowett J, Kangas AJ, Kasturiratne A, Kato N, Kotea N, Kowlessur S, Pitkäniemi J, Punjabi P, Saleheen D, Schafmayer C, Soininen P, Tai ES, Thorand B, Tuomilehto J, Wickremasinghe AR, Kyrtopoulos SA, Aitman TJ, Herder C, Hampe J, Cauchi S, Relton CL, Froguel P, Soong R, Vineis P, Jarvelin MR, Scott J, Grallert H, Bollati V, Elliott P, McCarthy M, Kooner JS (2015) Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study. Lancet Diabetes Endocrinol 3(7):526–534.  https://doi.org/10.1016/S2213-8587(15)00127-8 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lu H, Liu X, Deng Y, Qing H (2013) DNA methylation, a hand behind neurodegenerative diseases. Front. Aging Neurosci 5:85.  https://doi.org/10.3389/fnagi.2013.00085 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kader F, Ghai M, Maharaj L (2018) The effects of DNA methylation on human psychology. Behav Brain Res 346:47–65.  https://doi.org/10.1016/j.bbr.2017.12.004 CrossRefPubMedGoogle Scholar
  16. 16.
    Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14(1):R47–R58.  https://doi.org/10.1093/hmg/ddi114 CrossRefPubMedGoogle Scholar
  17. 17.
    Ciccarone F, Tagliatesta S, Caiafa P, Zampieri M (2018) DNA methylation dynamics in aging: how far are we from understanding the mechanisms? Mech Ageing Dev 174:3–17.  https://doi.org/10.1016/j.mad.2017.12.002 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Messerschmidt DM, Knowles BB, Solter D (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 28:812–828.  https://doi.org/10.1101/gad.234294.113 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Schmitz RJ, Schultz MD, Lewsey MG, O'Malley RC, Urich MA, Libiger O, Schork NJ, Ecker JR (2011) Transgenerational epigenetic instability is a source of novel methylation variants. Science 334(6054):369–373.  https://doi.org/10.1126/science.1212959 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Stricker SH, Götz M (2018) DNA-Methylation: Master or Slave of Neural Fate Decisions? Front Neuro 12:5.  https://doi.org/10.3389/fnins.2018.00005 CrossRefGoogle Scholar
  21. 21.
    van Dongen J, Nivard MG, Willemsen G, Hottenga JJ, Helmer Q, Dolan CV, Ehli EA, Davies GE, van Iterson M, Breeze CE, Beck S, BIOS Consortium, Suchiman HE, Jansen R, van Meurs J, Heijmans BT, Slagboom PE, Boomsma DI (2016) Genetic and environmental influences interact with age and sex in shaping the human methylome. Nat Commun 7:11115.  https://doi.org/10.1038/ncomms11115 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    King-Batoon A, Leszczynska JM, Klein CB (2008) Modulation of gene methylation by genistein or lycopene in breast cancer cells. Environ Mol Mutagen 49:36–45.  https://doi.org/10.1002/em.20363 CrossRefPubMedGoogle Scholar
  23. 23.
    Perrier F, Viallon V, Ambatipudi S, Ghantous A, Cuenin C, Hernandez-Vargas H, Chajès V, Baglietto L, Matejcic M, Moreno-Macias H, Kühn T, Boeing H, Karakatsani A, Kotanidou A, Trichopoulou A, Sieri S, Panico S, Fasanelli F, Dolle M, Onland-Moret C, Sluijs I, Weiderpass E, Quirós JR, Agudo A, Huerta JM, Ardanaz E, Dorronsoro M, Tong TYN, Tsilidis K, Riboli E, Gunter MJ, Herceg Z, Ferrari P, Romieu I (2019) Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study. Clin Epigenetics 11(1):57.  https://doi.org/10.1186/s13148-019-0637-x CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Alegria-Torres TAA, Baccarelli A, Bolati V (2011) Epigenetics and Lifestyle. Epigenomics. 3:267–277.  https://doi.org/10.2217/epi.11.22 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Elliott HR, Tillin T, McArdle WL, Ho K, Duggirala A, Frayling TM, Davey Smith G, Hughes AD, Chaturvedi N, Relton CL (2014) Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clin Epigenetics 6(1):4.  https://doi.org/10.1186/1868-7083-6-4 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Tsaprouni LG, Yang TP, Bell J, Dick KJ, Kanoni S, Nisbet J, Viñuela A, Grundberg E, Nelson CP, Meduri E, Buil A, Cambien F, Hengstenberg C, Erdmann J, Schunkert H, Goodall AH, Ouwehand WH, Dermitzakis E, Spector TD, Samani NJ, Deloukas P (2014) Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics. 9(10):1382–1396.  https://doi.org/10.4161/15592294.2014.969637 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Nielsen DA, Yuferov V, Hamon S, Jackson C, Ho A, Ott J, Kreek MJ (2009) Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts. Neuropsychopharmacology 34(4):867–873.  https://doi.org/10.1038/npp.2008.108 CrossRefPubMedGoogle Scholar
  28. 28.
    Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115.  https://doi.org/10.1186/gb-2013-14-10-r115 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Phipson B, Oshlack A (2014) DiffVar: a new method for detecting differential variability with application to methylation in cancer and aging. Genome Biol 15(9):465.  https://doi.org/10.1186/s13059-014-0465-4 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C, Greally JM, Barzilai N (2010) Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9(4):506–518.  https://doi.org/10.1111/j.1474-9726.2010.00577.x CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Florath I, Butterbach K, Müller H, Bewerunge-Hudler M, Brenner H (2014) Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Hum Mol Genet 23(5):1186–1201.  https://doi.org/10.1093/hmg/ddt531 CrossRefPubMedGoogle Scholar
  32. 32.
    Day K, Waite LL, Thalacker-Mercer A, West A, Bamman MM, Brooks JD et al (2013) Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol 14(9):R102.  https://doi.org/10.1038/npp.2008.108 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL et al (2016) Ageing and environmental exposures alter tissue-specific DNA methylation dependent on CpG island context. PLoS Genet 5(8):e1000602.  https://doi.org/10.1371/journal.pgen.1000602 CrossRefGoogle Scholar
  34. 34.
    Dmitrijeva M, Ossowski S, Serrano L, Schaefer MH (2018) Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates. Nucleic Acids Res 46(14):7022–7039.  https://doi.org/10.1093/nar/gky498 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kader F, Ghai M (2015) DNA Methylation and Application in Forensic Sciences. Forensic Sci Int 249:245–265.  https://doi.org/10.1016/j.forsciint.2015.01.037 CrossRefGoogle Scholar
  36. 36.
    Prokhortchouk E, Defossez PA (2008) The cell biology of DNA methylation in mammals. Biochim Biophys Acta 1783(11):2167–2173.  https://doi.org/10.1016/j.bbamcr.2008.07.015 CrossRefPubMedGoogle Scholar
  37. 37.
    Jjingo D, Conley AB, Yi SV, Lunyak VV, Jordan IK (2012) On the presence and role of human gene-body DNA methylation. Oncotarget 3(4):462–474.  https://doi.org/10.18632/oncotarget.497 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Illingworth RS, Bird AP (2009) CpG islands--'a rough guide'. FEBS Lett 583(11):1713–1720.  https://doi.org/10.1016/j.febslet.2009.04.012 CrossRefPubMedGoogle Scholar
  39. 39.
    Mendizabal I, Yi SV (2016) Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation. Hum Mol Genet 25(1):69–82.  https://doi.org/10.1093/hmg/ddv449 CrossRefPubMedGoogle Scholar
  40. 40.
    Edgar R, Tan PP, Portales-Casamar E, Pavlidis P (2014) Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression. Epigenetics Chromatin 7(1):28.  https://doi.org/10.1186/1756-8935-7-28 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Sijen T (2014) Molecular approaches for forensic cell type identification: On mRNA, miRNA, DNA methylation and microbial markers. Forensic Sci Int Genet 18:21–32.  https://doi.org/10.1016/j.fsigen.2014.11.015 CrossRefPubMedGoogle Scholar
  42. 42.
    Rechache NS, Wang Y, Stevenson HS, Killian JK, Edelman DC, Merino M et al (2012) DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors. J Clin Endocrinol Metab 97(6):E1004–E1013.  https://doi.org/10.1210/jc.2011-3298 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lokk K, Modhukur V, Rajashekar B, Märtens K, Mägi R, Kolde R, Koltšina M, Nilsson TK, Vilo J, Salumets A, Tõnisson N (2014) DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome Biol 15(4):r54.  https://doi.org/10.1186/gb-2014-15-4-r54 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    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. Nature Genet 38:1378–1385.  https://doi.org/10.1038/ng1909 CrossRefPubMedGoogle Scholar
  45. 45.
    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. Biochemical and Biophysical Research Communications. 376:658–664.  https://doi.org/10.1016/j.bbrc.2008.09.044 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cohen NM, Kenigsberg E, Tanay A (2011) Primate CpG Islands are maintained by Heterogeneous Evolutionary Regimes Involving Minimal Selection. Cell. 145:773–786.  https://doi.org/10.1016/j.cell.2011.04.024 CrossRefPubMedGoogle Scholar
  47. 47.
    Ohgane J, Yagi S, Shiota K (2008) Epigenetics: the DNA methylation profile of tissue-dependent and differentially methylated regions in cells. Placenta 29(Suppl A):S29–S35.  https://doi.org/10.1016/j.placenta.2007.09.011 CrossRefPubMedGoogle Scholar
  48. 48.
    Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Graf S et al (2008) An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 18:1518–1529.  https://doi.org/10.1101/gr.077479.108 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LTY, Kohlbacher O, de Jager PL, Rosen ED, Bennett DA, Bernstein BE, Gnirke A, Meissner A (2013) Charting a dynamic DNA methylation landscape of the human genome. Nature 500(7463):477–481.  https://doi.org/10.1038/nature12433 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Kayser M, de Knijff P (2011) Improving human forensics through advances in genetics, genomics and molecular biology. Nat Rev Genet 12(3):179–192.  https://doi.org/10.1038/nrg2952 CrossRefPubMedGoogle Scholar
  51. 51.
    Weyerman C, Ribaux O (2012) Situating forensic traces in time. Sci Justice 52:68–75.  https://doi.org/10.1016/j.scijus.2011.09.003 CrossRefGoogle Scholar
  52. 52.
    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 188:1–17.  https://doi.org/10.1016/j.forsciint.2009.02.013 CrossRefPubMedGoogle Scholar
  53. 53.
    An JH, Shin KJ, Yang WI, Lee HY (2012) Body fluid identification in forensics. BMB Rep 45:545–553.  https://doi.org/10.5483/BMBRep.2012.45.10.206 CrossRefPubMedGoogle Scholar
  54. 54.
    Quinone I, Daniel B (2012) Cell free DNA as a component of forensic evidence recovered from touched surfaces. Forensic Sci Int Genet 6(1):26–30.  https://doi.org/10.1016/j.fsigen.2011.01.004 CrossRefGoogle Scholar
  55. 55.
    An JH, Choi A, Shin KJ, Yang WI, Lee HY (2013) DNA methylation-specific multiplex assays for body fluid identification. Int J Legal Med 127:35–43.  https://doi.org/10.1007/s00414-012-0719-1 CrossRefPubMedGoogle Scholar
  56. 56.
    Choi A, Shin KJ, Yang WI, Lee HY (2014) Body fluid identification by integrated analysis of DNA methylation and body fluid-specific microbial DNA. Int J Legal Med 128(1):33–41.  https://doi.org/10.1007/s00414-013-0918-4 CrossRefPubMedGoogle Scholar
  57. 57.
    Vidaki A, Kayser M (2018) Recent progress, methods and perspectives in forensic epigenetics. Forensic Sci Int Genet 37:180–195.  https://doi.org/10.1016/j.fsigen.2018.08.008 CrossRefPubMedGoogle Scholar
  58. 58.
    Frumkin D, Wasserstrom A, Budowle B, Davidson A (2011) DNA methylation-based forensic tissue identification. Forensic Sci Int Genet 5:517–524.  https://doi.org/10.1016/j.fsigen.2010.12.001 CrossRefPubMedGoogle Scholar
  59. 59.
    Lee HY, An JH, Jung SE, Oh YN, Lee EY, Choi A, Yang WI, Shin KJ (2015) Genome-wide methylation profiling and a multiplex construction for the identification of body fluids using epigenetic markers. Forensic Sci Int Genet 17:17–24.  https://doi.org/10.1016/j.fsigen.2015.03.002 CrossRefPubMedGoogle Scholar
  60. 60.
    Lee HY, Jung SE, Lee EH, Yang WI, Shin KJ (2016) DNA methylation profiling for a confirmatory test for blood, saliva, semen, vaginal fluid and menstrual blood. Forensic Sci Int Genet 24:75–82.  https://doi.org/10.1016/j.fsigen.2016.06.007 CrossRefPubMedGoogle Scholar
  61. 61.
    Holtkotter H, Beyer V, Schwender K, Glaub A, Johann KS, Schurenkamp M et al (2017) Independent validation of body fluid-specific CpG markers and construction of a robust multiplex assay. Forensic Sci Int Genet 29:261–268.  https://doi.org/10.1016/j.fsigen.2017.05.002 CrossRefPubMedGoogle Scholar
  62. 62.
    Lin YC, Tsai LC, Lee JC, Liu KL, Tzen JT, Linacre A et al (2016) Novel identification of biofluids using a multiplex methylation-specific PCR combined with single-base extension system. Forensic Sci Med Pathol 12(2):128–138.  https://doi.org/10.1007/s12024-016-9763-3 CrossRefPubMedGoogle Scholar
  63. 63.
    Silva DSBS, Antunes J, Balamurugan K, Duncan G, Alho CS, McCord B (2016) Developmental validation studies of epigenetic DNA methylation markers for the detection of blood, semen and saliva samples. Forensic Sci Int Genet 23:55–63.  https://doi.org/10.1016/j.fsigen.2016.01.017 CrossRefPubMedGoogle Scholar
  64. 64.
    Peat JR, Smallwood SA (2018) Low Input Whole-Genome Bisulfite Sequencing Using a Post-Bisulfite Adapter Tagging Approach. Methods Mol Bio 1708:161–169.  https://doi.org/10.1007/978-1-4939-7481-8_9 CrossRefGoogle Scholar
  65. 65.
    Darst RP, Pardo CE, Ai L, Brown KD, Kladde MP (2010) Bisulfite sequencing of DNA. Curr Protoc Mol Biol. Chapter 7 Unit 7.9.1-17. DOI:  https://doi.org/10.1002/0471142727.mb0709s91.CrossRefGoogle Scholar
  66. 66.
    Gomes I, Kohlmeier F, Schneider PM (2011) Genetic markers for body fluid and tissue identification in forensics. Forensic Sci Int Genet Suppl Ser 3:e469–e470.  https://doi.org/10.1016/j.fsigss.2011.09.096 CrossRefGoogle Scholar
  67. 67.
    Madi T, Balamurugan K, Bombardi R, Duncan G, McCord B (2012) The determination of tissue specific DNA methylation patterns in forensic biofluids using bisulphite modification and pyrosequencing. Electrophoresis 33:1736–1745.  https://doi.org/10.1002/elps.201100711 CrossRefPubMedGoogle Scholar
  68. 68.
    Antunes J, Madi T, Balamurugan K, Bombardi R, Duncan G, McCord B (2013) DNA methylation markers as a powerful technique to discriminate body fluids present in crime scenes. Available at: http://au.promega.com/~/media/files/resources/conference%20proceedings/ishi%2024/oral%20presentations/antunes-manuscript.pdf. [Downloaded 25 May 2014].
  69. 69.
    Lee HY, Park MJ, Choi A, An JH, Yang WI, Shin KJ (2012) Potential forensic application of DNA methylation profiling to body fluid identification. Int J Legal Med 126:55–62.  https://doi.org/10.1007/s00414-011-0569-2 CrossRefPubMedGoogle Scholar
  70. 70.
    Kitamura E, Igarashi J, Morohashi A, Hida N, Oinuma T, Nemoto N et al (2007) Analysis of tissue-specific differentially methylated regions (TDMs) in humans. Genomics 89:326–337.  https://doi.org/10.1016/j.ygeno.2006.11.006 CrossRefPubMedGoogle Scholar
  71. 71.
    Illingworth RS, Kerr A, DeSousa D, Jorgensen H, Ellis P, Stalker J et al (2008) A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biology 6:e22.  https://doi.org/10.1371/journal.pbio.0060022 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Park JL, Kwon OH, Kim JH, Yoo HS, Lee HC, Woo KM, Kim SY, Lee SH, Kim YS (2014) Identification of body fluid specific DNA methylation markers for use in forensic science. Forensic Sci Int Genet 13:147–153.  https://doi.org/10.1016/j.fsigen.2014.07.011 CrossRefPubMedGoogle Scholar
  73. 73.
    Forat S, Huettel B, Reinhardt R, Fimmers R, Haidl G, Denschlag D, Olek K (2016) Methylation markers for the identification of body fluids and Tissues from forensic trace evidence. PLoS One 11(2):e0147973.  https://doi.org/10.1371/journal.pone.0147973 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Fu XD, Wu J, Wang J, Huang Y, Hou YP, Yan J (2015) Identification of body fluid using tissue-specific DNA methylation markers. Forensic Sci Int Genet Suppl Ser 5:e151–e153.  https://doi.org/10.1016/j.fsigss.2015.09.061 CrossRefGoogle Scholar
  75. 75.
    Watanabe K, Akutsu T, Takamura A, Sakurada K (2016) Evaluation of a blood-specific DNA methylated region and trial for allele-specific blood identification from mixed body fluid DNA. Legal Med (Tokyo, Japan) 22:49–53.  https://doi.org/10.1016/j.legalmed.2016.08.004 CrossRefGoogle Scholar
  76. 76.
    Vidaki A, Giangasparo F, Syndercombe Court D (2016) Discovery of potential DNA methylation markers for forensic tissue identification using bisulphite pyrosequencing. Electrophoresis 37(21):2767–2779.  https://doi.org/10.1002/elps.201600261 CrossRefPubMedGoogle Scholar
  77. 77.
    Antunes J, Silva DS, Balamurugan K, Duncan G, Alho CS, McCord B (2015) High-resolution melt analysis of DNA to discriminate semen in biological stains. Anal Biochem 494:40–45.  https://doi.org/10.1016/j.ab.2015.10.002 CrossRefPubMedGoogle Scholar
  78. 78.
    Matheson CD, Gurney C, Esau N, Lehto R (2010) Assessing PCR Inhibition from Humic Substances. Open Enzyme Inhib J 3:38–45.  https://doi.org/10.2174/1874940201003010038 CrossRefGoogle Scholar
  79. 79.
    Li LC, Dahiya R (2002) MethPrimer: designing primers for methylation PCRs. Bioinformatics 18(11):1427–1431.  https://doi.org/10.1093/bioinformatics/18.11.1427 CrossRefPubMedGoogle Scholar
  80. 80.
    Chaitanya L, Van Oven M, Weiler N, Harteveld J, Wirken L, Sijen T et al (2014) Developmental validation of mitochondrial DNA genotyping assays for adept matrilineal inference of biogeographic ancestry at a continental level. Forensic Sci Int Genet 11:39–51.  https://doi.org/10.1016/j.fsigen.2014.02.010 CrossRefPubMedGoogle Scholar
  81. 81.
    Antunes J, Silva DS, Balamurugan K, Duncan G, Alho CS, McCord B (2016) Forensic discrimination of vaginal epithelia by DNA methylation analysis through pyrosequencing. Electrophoresis 37(21):2751–2758.  https://doi.org/10.1002/elps.201600037 CrossRefPubMedGoogle Scholar
  82. 82.
    Esteller M, Herman JG (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196:1–7.  https://doi.org/10.1002/path.1024 CrossRefPubMedGoogle Scholar
  83. 83.
    Zhang D, Cheng L, Badner JA, Chen C, Chen Q, Luo W, Craig DW, Redman M, Gershon ES, Liu C (2010) Genetic control of individual differences in gene-specific methylation in human brain. Am J Hum Genet 86(3):411–419.  https://doi.org/10.1016/j.ajhg.2010.02.005 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H, Whittaker P, McCann O, Finer S, Valdes AM, Leslie RD, Deloukas P, Spector TD (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20(4):434–439.  https://doi.org/10.1101/gr.103101.109 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Kaminsky Z, Petronis A (2009) Methylation SNaPshot: a method for the quantification of site-specific DNA methylation levels. Methods Mol Biol 507:241–255.  https://doi.org/10.1007/978-1-59745-522-0_18 CrossRefPubMedGoogle Scholar
  86. 86.
    Subramanian S, Kumar S (2003) Neutral Substitutions Occur at a Faster Rate in Exons than in Noncoding DNA in Primate Genomes. Genome Res 13(5):838–844. DOI: 10.1186/1756-8935-6-26. DOI:  https://doi.org/10.1101/gr.1152803.CrossRefGoogle Scholar
  87. 87.
    Chatterjee S, Pal JK (2009) Role of 5'- and 3'-untranslated regions of mRNAs in human diseases. Biol Cell 101(5):251–262.  https://doi.org/10.1042/BC20080104 CrossRefPubMedGoogle Scholar
  88. 88.
    Reamon-Buettner SM, Cho SH, Borlak J (2007) Mutations in the 3’-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD). BMC Medical Genetics 8:38.  https://doi.org/10.1186/1471-2350-8-38 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Rogozin IB, Pavlov YI (2003) Theoretical analysis of mutation hotspots and their DNA sequence context specificity. Mutat Res 544(1):65–85CrossRefGoogle Scholar
  90. 90.
    Baer CF, Miyamoto MM, Denver DR (2007) Mutation rate variation in multicellular eukaryotes: Causes and consequences. Nat Rev Genet 8:619–631.  https://doi.org/10.1038/nrg2158 CrossRefPubMedGoogle Scholar
  91. 91.
    Duret L (2009) Mutation patterns in the human genome: More variable than expected. PLoS Biology 7(2):e1000028.  https://doi.org/10.1371/journal.pbio.100002 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Arndt PF, Hwa T, Petrov DA (2005) Substantial regional variation in substitution rates in the human genome: Importance of GC content, gene density, and telomere-specific effects. J Mol Evol 60:748–763.  https://doi.org/10.1007/s00239-004-0222-5 CrossRefPubMedGoogle Scholar
  93. 93.
    Duret L, Arndt PF (2008) The impact of recombination on nucleotide substitutions in the human genome. PLoS Genetics 4(5):e1000071.  https://doi.org/10.1371/journal.pgen.1000071 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Nabel CS, Manning SA, Kohli RM (2012) The Curious Chemical Biology of Cytosine: Deamination, Methylation and Oxidation as Modulators of Genomic Potential. ACS Chem Biol 7(1):20–30.  https://doi.org/10.1021/cb2002895 CrossRefPubMedGoogle Scholar
  95. 95.
    Frederico LA, Kunkel TA, Shaw BR (1993) Cytosine deamination in mismatched base pairs. Biochemistry 32:6523–6530.  https://doi.org/10.1021/bi00077a005 CrossRefPubMedGoogle Scholar
  96. 96.
    Fryxell KJ, Moon WJ (2005) CpG mutation rates in the human genome are highly dependent on local GC content. Mol Biol Evol 22(3):650–658.  https://doi.org/10.1093/molbev/msi131 CrossRefPubMedGoogle Scholar
  97. 97.
    Duret L, Semon M, Piganeau G, Mouchiroud D, Galtier N (2002) Vanishing GC-rich isochores in mammalian genomes. Genetics 162:1837–1847 PMC1462357PubMedPubMedCentralGoogle Scholar
  98. 98.
    Keightley PD, Eyre-Walker A (2000) Deleterious mutations and the evolution of sex. Science 5490:331–333.  https://doi.org/10.1126/science.290.5490.331 CrossRefGoogle Scholar
  99. 99.
    Martinez-Arias R, Calafell F, Mateu E, Comas D, Andres A, Bertranpetit J (2001) Sequence variability of a human pseudogene. Genome Res 11:1071–1085.  https://doi.org/10.1101/gr.167701 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Nachman MW, Crowell SL (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156:297–304 PMC1461236PubMedPubMedCentralGoogle Scholar
  101. 101.
    Chen FC, Vallender EJ, Wang H, Tzeng CS, Li WH (2001) Genomic divergence between human and chimpanzee estimated from large-scale alignments of genomic sequences. J Hered 92:481–489.  https://doi.org/10.1093/jhered/92.6.481 CrossRefPubMedGoogle Scholar
  102. 102.
    Mathews DJ, Kashuk C, Brightwell G, Eichler EE, Chakravarti A (2001) Sequence variation within the fragile X locus. Genome Res 11:1382–1391.  https://doi.org/10.1101/gr.172601 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Yu N, Zhao Z, Fu YX, Sambuughin N, Ramsay M, Jenkins T, Leskinen E, Patthy L, Jorde LB, Kuromori T, Li WH (2001) Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1. Mol Biol Evol 18:214–222.  https://doi.org/10.1093/oxfordjournals.molbev.a003795 CrossRefPubMedGoogle Scholar
  104. 104.
    Botstein D, Risch N (2003) Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet 33:228–237.  https://doi.org/10.1038/ng1090 CrossRefPubMedGoogle Scholar
  105. 105.
    Ng PC, Levy S, Huang J, Stockwell TB, Walenz BP, Li K, Axelrod N, Busam DA, Strausberg RL, Venter JC (2008) Genetic Variation in an Individual Human Exome. PLoS Genetics 4(8):e1000160CrossRefGoogle Scholar
  106. 106.
    Daca-Roszak P, Pfeifer A, Zebracka-Gala J, Rusinek D, Szybinska A, Jarzab B et al (2015) Impact of SNPs on methylation readouts by Illumina Infinium HumanMethylation450 BeadChip Array: implications for comparative population studies. BMC Genomics 16:1003.  https://doi.org/10.1186/s12864-015-2202-0 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Galanter JM, Gignoux CR, Oh SS, Pino-Yanes M, Thakur N, Eng C et al (2017) Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. eLife 6:e20532.  https://doi.org/10.7554/eLife.20532 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Dunn J, Thabet S, Jo H (2015) Flow-dependent epigenetic DNA methylation in endothelial gene expression and atherosclerosis. Arterioscler Thromb Vasc Biol 35(7):1562–1569.  https://doi.org/10.1161/ATVBAHA.115.305042 CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Tost J (2010) DNA Methylation: An Introduction to the Biology and the Disease-Associated Changes of a Promising Biomarker. Mol Biotech 44:71–81.  https://doi.org/10.1007/978-1-59745-522-0_1 CrossRefGoogle Scholar
  110. 110.
    Giuliani C, Sazzini M, Bacalini MG, Pirazzini C, Marasco E, Fontanesi E (2016) Epigenetic Variability across Human Populations: A Focus on DNA Methylation Profiles of the KRTCAP3, MAD1L1 and BRSK2 Genes. Genome Biol Evol 8(9):2760–2773.  https://doi.org/10.1093/gbe/evw186 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Terry MB, Ferris JS, Pilsner R, Flom JD, Tehranifar P, Sentellar RM et al (2008) Genomic DNA Methylation among Women in a Multiethnic New York City Birth Cohort. Cancer Epidemiol Biomarkers Prev 17:2306–2310.  https://doi.org/10.1158/1055-9965.EPI-08-0312 CrossRefPubMedGoogle Scholar
  112. 112.
    Zaghlool SB, Al-Shafai M, Al Muftah WA, Kumar P, Falchi M, Suhre K (2015) Association of DNA methylation with age, gender, and smoking in an Arab population. Clin Epigenetics 7(1):6.  https://doi.org/10.1186/s13148-014-0040-6 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Reed K, Poulin ML, Yan L, Parissenti AM (2010) Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. Anal Biochem 397(1):96–106.  https://doi.org/10.1016/j.ab.2009.10.021 CrossRefPubMedGoogle Scholar
  114. 114.
    Wojdacz TK, Møller TH, Thestrup BB, Kristensen LS, Hansen LL (2010) Limitations and advantages of MS-HRM and bisulfite sequencing for single locus methylation studies. Expert Rev Mol Diagn 10(5):575–580.  https://doi.org/10.1586/erm.10.46 CrossRefPubMedGoogle Scholar
  115. 115.
    Wreczycka K, Gosdschan A, Yusuf D, Grüning B, Assenov Y, Akalin A (2017) Strategies for analyzing bisulfite sequencing data. J Biotechnol 261:105–115.  https://doi.org/10.1016/j.jbiotec.2017.08.007 CrossRefPubMedGoogle Scholar
  116. 116.
    Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R, Degner JF et al (2011) DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol 12:1–13.  https://doi.org/10.1186/gb-2011-12-1-r10 CrossRefGoogle Scholar
  117. 117.
    Schalkwyk LC, Meaburn EL, Smith R, Dempster EL, Jeffries AR, Davies MN, Plomin R, Mill J (2010) Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet 86(2):196–212.  https://doi.org/10.1016/j.ajhg.2010.01.014 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Cooper DN (2010) Functional intronic polymorphisms: buried treasure awaiting discovery within our genes. Hum Genomics 4:284.  https://doi.org/10.1186/1479-7364-4-5-284 CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy M, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll S, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461:747–753.  https://doi.org/10.1038/nature08494 CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Gervin K, Hammero M, Akselsen HE, Moe R, Nygard H, Brandt I et al (2011) Extensive variation and low heritability of DNA methylation identified in a twin study. Genome Res 21:1813–1821.  https://doi.org/10.1101/gr.119685.110 CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Bell JT, Tsai PC, Yang TP, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, Shin SY, Dempster EL, Murray RM, Grundberg E, Hedman AK, Nica A, Small KS, MuTHER Consortium, Dermitzakis ET, McCarthy M, Mill J, Spector TD, Deloukas P (2012) Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genetics 8(4):e1002629.  https://doi.org/10.1371/journal.pgen.1002629 CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Boks MP, Derks EM, Weisenberger DJ, Strengman E, Janson E, Sommer IE et al (2009) The relationship of DNA methylation with age, gender and genotype in twins and healthy controls. PLoS One 4:6767.  https://doi.org/10.1371/journal.pone.0006767 CrossRefGoogle Scholar
  123. 123.
    Breton CV, Salam MT, Gilliland FD (2011) Heritability and role for the environment in DNA methylation in AXL receptor tyrosine kinase. Epigenetics 6(7):895–898.  https://doi.org/10.4161/epi.6.7.15768 CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Gibbs JR, van der Brug MP, Hernandez DG, Traynor BJ, Nalls MA, Lai SL, Arepalli S, Dillman A, Rafferty IP, Troncoso J, Johnson R, Zielke HR, Ferrucci L, Longo DL, Cookson MR, Singleton AB (2010) Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genetics 6(5):e1000952.  https://doi.org/10.1371/journal.pgen.1000952 CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Quon G, Lippert C, Heckerman D, Listgarten J (2013) Patterns of methylation heritability in a genome-wide analysis of four brain regions. Nucleic Acids Res 41(4):2095–2104.  https://doi.org/10.1093/nar/gks1449 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Rowlatt A, Hernández-Suárez G, Sanabria-Salas MC, Serrano-López M, Rawlik K, Hernandez-Illan E, Alenda C, Castillejo A, Soto JL, Haley CS, Tenesa A (2016) The heritability and patterns of DNA methylation in normal human colorectum. Hum Mol Genet 25(12):2600–2611.  https://doi.org/10.1093/hmg/ddw072 CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Zbiec-Piekarska R, Spolnicka M, Kupiec T, Makowska Z, Spas A, Parys-Proszek A et al (2015) Examination of DNA methylation status of the ELOVL2 marker may be useful for human age prediction in forensic science. Forensic Sci Int Genet 14:161–167.  https://doi.org/10.1016/j.fsigen.2014.10.002 CrossRefPubMedGoogle Scholar
  128. 128.
    Thong Z, Chan XLS, Tan JYY, Loo ES, Syn CKC (2017) Evaluation of DNA methylation-based age prediction on blood. Forensic Sci Int Genet Suppl Series 6:e249–e251.  https://doi.org/10.1016/j.fsigss.2017.09.095 CrossRefGoogle Scholar
  129. 129.
    Park J-L, Kim JH, Seo E, Bae DH, Kim S-Y, Lee H-C et al (2016) Identification and evaluation of age-correlated DNA methylation markers for forensic use. Forensic Sci Int Genet 23:64–70.  https://doi.org/10.1016/j.fsigen.2016.03.005 CrossRefPubMedGoogle Scholar
  130. 130.
    Vidaki A, Ballard D, Aliferi A, Miller TH, Barron LP, Syndercombe Court D (2017) DNA methylation-based forensic age prediction using artificial neural networks and next generation sequencing. Forensic Sci Int Genet 28:225–236.  https://doi.org/10.1016/j.fsigen.2017.02.009 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering and ScienceUniversity of KwaZulu-Natal (Westville Campus)DurbanRepublic of South Africa
  2. 2.Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and ScienceUniversity of KwaZulu-Natal (Westville Campus)DurbanRepublic of South Africa

Personalised recommendations