Advertisement

Traces of Life’s Experiences: Epigenetics (DNA methylation) in Forensics

  • Meenu GhaiEmail author
  • Dyfed Lloyd Evans
  • Shailesh Joshi
Reference work entry

Abstract

Since the development of methylation-based diagnostic biomarkers, the application of DNA methylation in forensic investigation is also rapidly gaining ground. DNA methylation patterns are established during early embryonic development and are influenced by both genetic and environmental factors like diet, age, stress, socioeconomic status, and habitat. Identification of differentially methylated regions (DMRs) which differ between tissues or phenotypes can be targeted for forensic applications. Tissue-specific methylation differences can be used for accurate identification of body fluid/ tissue source found at a crime scene. Age-specific methylation changes in repetitive genomic regions have been used to develop epigenetic clocks for age estimation. DNA methylation patterns differ even between monozygotic twins and can assist with the challenge of their identification. Recent development of whole genome methylation analysis platforms like Illumina whole genome methylation bead chips and single-cell reduced bisulfite sequencing has opened the doors for large-scale survey of methylation differences in both CpG islands and non-CpG regions. Future research could predict an individual’s social behavior and activities by applying DNA methylation indicators. Advancements in DNA methylation analysis for forensics will complement the current STR analysis and provide robust inferences for forensic evidence and human identification.

Keywords

DNA methylation Forensics Differentially methylated regions (DMRs) Tissue-specific differentially methylated regions (tDMRs) Body fluid identification Monozygotic twins Forensic age estimation Behavioral epigenetics Population epigenetics 

List of Abbreviations

CpG

Cytosine–phosphate–guanine

DmAM

DNA methylation age measures

DMRs

Differentially methylated regions

DNAm

DNA methylation

DZ

Dizygotic

ICR

Imprinting control regions

LINE-1

Long interspersed elements

MeCAP-seq

Methylated DNA capture by affinity purification sequencing

MeDIP-seq

Methylated DNA immunoprecipitation sequencing

MSRE-PCR

Methylation-specific restriction enzyme polymerase chain reaction

MS-SNuPE

Methylation-sensitive single-nucleotide primer extension

MZ

Monozygotic

sjTRECs

Signal joint TCR excision circles

SNP

Single-nucleotide polymorphism

STR

Simple sequence repeat

WGBS

Whole genome bisulfite sequencing

References

  1. Adkins RM, Krushkal J, Tylavsky FA, Thomas F (2011) Racial differences in gene-specific DNA methylation levels are present at birth. Birth Defects Res Part A Clin Mol Teratol 91:728–736CrossRefGoogle Scholar
  2. An JH, Choi A, Shin KJ et al (2013) DNA methylation specific multiplex assays for body fluid identification. Int J Legal Med 127:35CrossRefGoogle Scholar
  3. Bai L, Yan P, Cao X et al (2015) Methylation-sensitive restriction enzyme nested real time PCR, a potential approach for sperm DNA identification. J Forensic Legal Med 34:34–39CrossRefGoogle Scholar
  4. Barrett EL, Burke TA, Hammers M et al (2013) Telomere length and dynamics predict mortality in a wild longitudinal study. Mol Ecol 22:249–259CrossRefGoogle Scholar
  5. Bekaert B, Kamalandua A, Zapico S et al (2015) Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. Epigenetics 10:922–930CrossRefGoogle Scholar
  6. Bennett DA, Yu L, Yang J et al (2015) Epigenomics of Alzheimer’s disease. Transl Res 165:200–220CrossRefGoogle Scholar
  7. Berdasco M, Esteller M (2012) Hot topics in epigenetic mechanisms of aging. Aging Cell 11:181–186CrossRefGoogle Scholar
  8. Bocklandt S, Lin W, Sehl ME et al (2011) Epigenetic predictor of age. PLoS One 22:e14821CrossRefGoogle Scholar
  9. Cappetta M, Berdasco M, Hochmann J et al (2015) Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. BMC Cancer 15:1CrossRefGoogle Scholar
  10. Castellani CA, Laufer BI, Melka MG et al (2015) DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks. BMC Med Genet 8(1):1Google Scholar
  11. 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):33–41CrossRefGoogle Scholar
  12. Cordova-Palomera A, Fatjo-Vilas M, Gasto C et al (2015) Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins. Transl Psychiatry 5(4):e557CrossRefGoogle Scholar
  13. Craig JM (2010) Epigenetic studies of a newborn twin cohort: insights into prenatal development. Twin Res Hum Genet 13:252Google Scholar
  14. Dempster EL, Pidsley R, Schalkwyk LC et al (2011) Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 20:4786–4796.  https://doi.org/10.1093/hmg/ddr416CrossRefPubMedPubMedCentralGoogle Scholar
  15. Du Q, Zhu G, Fu G et al (2015) A genome wide scan of DNA methylation markers for distinguishing monozygotic twins. Twin Res Hum Genet 18:670–679CrossRefGoogle Scholar
  16. Eckhardt F, Lewin J, Cortese R et al (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38:1378–1385CrossRefGoogle Scholar
  17. Eriksson A, Manica A (2012) Effect of ancient population structure on the degree of polymorphism shared between modern human populations and ancient Hominins. Proc Natl Acad Sci 109:13956–13960CrossRefGoogle Scholar
  18. Feng J, Zhou Y, Campbell SL et al (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430CrossRefGoogle Scholar
  19. Florath I, Butterbach K, Muller H et al (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 23:1186–1201CrossRefGoogle Scholar
  20. Forat S, Huettel B, Reinhardt R et al (2016) Methylation markers for the identification of body fluids and tissues from forensic trace evidence. PLoS One 11(2):e0147973CrossRefGoogle Scholar
  21. Fraga MF, Ballestar E, Paz MF, Ropero S et al (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102:10604–10609CrossRefGoogle Scholar
  22. Fraser HB, Lam LL, Neumann SM, Kobor MS (2012) Population-specificity of human DNA methylation. Genome Biol 13:1CrossRefGoogle Scholar
  23. Frumkin D, Wasserstrom A, Davidson A, Grafit A (2010) Authentication of forensic DNA samples. Forensic Sci Int Genet 4(2):95–103CrossRefGoogle Scholar
  24. Gunter TD (2015) Behavioral genetics and the forensic mental health provider: an overview. Behav Sci Law 33:598–606CrossRefGoogle Scholar
  25. Haas C, Hanson E, Anjos MJ et al (2014) RNA/DNA co-analysis from human menstrual blood and vaginal secretion stains: results of a fourth and fifth collaborative EDNAP exercise. Forensic Sci Int Genet 8(1):203–212CrossRefGoogle Scholar
  26. Hanson EK, Lubenow H, Ballantyne J (2009) Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal Biochem 387(2):303–314CrossRefGoogle Scholar
  27. Hernando-Herraez I, Garcia-Perez R, Sharp AJ et al (2015) DNA methylation: insights into human evolution. PLoS Genet 11:e1005661CrossRefGoogle Scholar
  28. Heyn H, Moran S, Hernando-Herraez I et al (2013) DNA methylation contributes to natural human variation. Genome Res 23:1363–1372CrossRefGoogle Scholar
  29. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115CrossRefGoogle Scholar
  30. Kaminsky ZA (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245CrossRefGoogle Scholar
  31. Kayser M, de Knijff P (2011) Improving human forensics through advances in genetics, genomics and molecular biology. Nat Rev Genet 12:179–192Google Scholar
  32. Koops BJ, Schellekens M (2008) Forensic DNA phenotyping: regulatory issues. C Sci Tech Law Rev 9:158Google Scholar
  33. Kwabi-Addo B, Wang S, Chung W et al (2010) Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men. Clin Cancer Res 16:3539–3547CrossRefGoogle Scholar
  34. Lattal KM, Abel T (2001) Different requirements for protein synthesis in acquisition and extinction of spatial preferences and context-evoked fear. J Neurosci 21:5773–5780CrossRefGoogle Scholar
  35. Lee HY, Park MJ, Choi A et al (2012) Potential forensic application of DNA methylation profile to body fluid identification. Int J Legal Med 126:55–62CrossRefGoogle Scholar
  36. Lee HY, Jung SE, Oh YN et al (2015) Epigenetic age signatures in the forensically relevant body fluid of semen: a preliminary study. Forensic Sci Int Genet 19:28–34CrossRefGoogle Scholar
  37. Lester BM, Tronick E, Nestler E et al (2011) Behavioral epigenetics. Ann N Y Acad Sci 1226:14–33CrossRefGoogle Scholar
  38. Li C, Zhao S, Zhang N et al (2013a) Differences of DNA methylation profiles between monozygotic twins’ blood samples. Mol Biol Rep 40(9):5275–5280Google Scholar
  39. Li X, Wei W, Ratnu VS et al (2013b) On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiol Learn Mem 105:125–132Google Scholar
  40. Lindbo JA, Dougherty WG (2005) Plant pathology and RNAi: a brief history. Annu Rev Phytopathol 43:191–204CrossRefGoogle Scholar
  41. Madi T, Balamurugan K, Bombardi R et al (2012) The determination of tissue-specific DNA methylation patterns in forensic biofluids using bisulfite modification and pyrosequencing. Electrophoresis 33(12):1736–1745CrossRefGoogle Scholar
  42. Maze I, Covinton HE, Dietz DM et al (2010) Essential roles of the histome methyltransferase G9a in cocaine-induced plasticity. Science 327:213–216CrossRefGoogle Scholar
  43. Meaney MJ, Ferguson-Smith AC (2010) Epigenetic regulation of the neural transcriptome: the meaning of the marks. Nat Neurosci 11:1313–1318CrossRefGoogle Scholar
  44. Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–859CrossRefGoogle Scholar
  45. Nielsen DA, Hamon S, Yuferov V et al (2010) Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts. Hum Genet 127:639–649CrossRefGoogle Scholar
  46. Ollikainen M, Smith KR, Joo EJ et al (2010) DNA methylation analysis of multiple tissues from new born twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum Mol Genet 19:4176–4188CrossRefGoogle Scholar
  47. Park JL, Kwon OH, Kim JH et al (2014) Identification of body fluid-specific DNA methylation markers for use in forensic science. Forensic Sci Int Genet 13:147–153CrossRefGoogle Scholar
  48. Peters TJ, Buckley MJ, Statham AL et al (2015) De novo identification of differentially methylated regions in the human genome. Epigenetics Chromatin 8:6PubMedPubMedCentralGoogle Scholar
  49. Pirazzini C, Giuliani C, Bacalini MG et al (2012) Space/population and time/age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono-and di-zygotic twins of different age. Aging 4(7):509–520CrossRefGoogle Scholar
  50. Rakyan VK, Down TA, Balding DJ et al (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet 12:529–541CrossRefGoogle Scholar
  51. Sijen T (2015) Molecular approaches for forensic cell type identification: on mRNA, miRNA, DNA methylation and microbial markers. Forensic Sci Int Genet 18:21–32CrossRefGoogle Scholar
  52. Terry MB, Ferris JS, Pilsner R et al (2008) Genomic DNA methylation among women in a multiethnic New York City birth cohort. Cancer Epidemiol Biomark Prev 17:2306–2310CrossRefGoogle Scholar
  53. Thevissen PW, Kaur J, Willems G (2012) Human age estimation combining third molar and skeletal development. Int J Legal Med 126:285–292CrossRefGoogle Scholar
  54. Van den Berge M, Carracedo A, Gomes I et al (2014) A collaborative European exercise on mRNA-based body fluid/skin typing and interpretation of DNA and RNA results. Forensic Sci Int Genet 10:40–48CrossRefGoogle Scholar
  55. Vidal-Bralo L, Lopez-Golan Y, Gonzalez A (2016) Simplified assay for epigenetic age estimation in whole blood of adults. Front Genet 7:126CrossRefGoogle Scholar
  56. Wang S, Dorsey TH, Terunuma A et al (2012) Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer. PLoS One 7(5):e37928CrossRefGoogle Scholar
  57. Wielscher M, Vierlinger K, Kegler U et al (2015) Diagnostic performance of plasma DNA methylation profiles in lung cancer, pulmonary fibrosis and COPD. EBioMedicine 2(8):929–936CrossRefGoogle Scholar
  58. Wittenberger T, Sleigh S, Reisel D et al (2014) DNA methylation markers for early detection of women’s cancer: promise and challenges. Epigenomics 6(3):311–327CrossRefGoogle Scholar
  59. Xu C, Qu H, Wang G et al (2015a) A novel strategy for forensic age prediction by DNA methylation and support vector regression model. Sci Rep 5:17788CrossRefGoogle Scholar
  60. Xu J, Fu G, Yan L et al (2015b) LINE-1 DNA methylation: a potential forensic marker for discriminating monozygotic twins. Forensic Sci Int Genet 19:136–145CrossRefGoogle Scholar
  61. Yong WS, Hsu FM, Chen PY (2016) Profiling genome-wide DNA methylation. Epigenetics Chromatin 9:26CrossRefGoogle Scholar
  62. Yuan T, Jiao Y, de Jong S et al (2015) An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging. PLoS Genet 11(2):e1004996CrossRefGoogle Scholar
  63. Zbieć-Piekarska R, Spólnicka M, Kupiec T 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 14:161–167CrossRefGoogle Scholar
  64. Ziller MJ, Gu H, Müller F et al (2013) Charting a dynamic DNA methylation landscape of the human genome. Nature 500(7463):477–481CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Meenu Ghai
    • 1
    Email author
  • Dyfed Lloyd Evans
    • 1
  • Shailesh Joshi
    • 1
  1. 1.School of Life SciencesUniversity of KwaZulu-Natal,Westville CampusDurbanSouth Africa

Personalised recommendations