Forensic Individual Age Estimation with DNA: From Initial Approaches to Methylation Tests

Forensic Science Review

Volumn 29, Issue 2, 2017, Pages 122-144

  Freire Aradas, A ^a   Phillips, C ^a   Lareu, M V ^a  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

Author keywords

Age estimation; Bisulfite conversion; DNA methylation; Epigenetic age; Epigenetic clock; Forensic; Statistical regression models. C

Indexed keywords

ACYLTRANSFERASE; ALPHA2 INTEGRIN; AMIDASE; ASPARTOACYLASE; EDAR ASSOCIATED DEATH DOMAIN PROTEIN; FATTY ACID ELONGASES; FHL2 PROTEIN, HUMAN; ITGA2B PROTEIN, HUMAN; LIM HOMEODOMAIN PROTEIN; MUSCLE PROTEIN; PDE4C PROTEIN, HUMAN; PHOSPHODIESTERASE IV; SULFITE; TRANSCRIPTION FACTOR;

AGING; CHEMISTRY; CPG ISLAND; DNA METHYLATION; DNA SEQUENCE; EPIGENETICS; FORENSIC GENETICS; GENETICS; HUMAN; PROCEDURES;

ACETYLTRANSFERASES; AGING; AMIDOHYDROLASES; CPG ISLANDS; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; DNA METHYLATION; EDAR-ASSOCIATED DEATH DOMAIN PROTEIN; EPIGENOMICS; FORENSIC GENETICS; HUMANS; INTEGRIN ALPHA2; LIM-HOMEODOMAIN PROTEINS; MUSCLE PROTEINS; SEQUENCE ANALYSIS, DNA; SULFITES; TRANSCRIPTION FACTORS;

EID: 85028683051     PISSN: 10427201     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (168)

1. REFERENCE: Freire-Aradas A, Phillips C, Lareu MV: Forensic individual age estimation with DNA: from initial approaches to methylation tests; Forensic Sci Rev 29:121; 2017.
2. Adaikalakoteswari A, Finer S, Voyias PD, McCarthy CM, Vatish M, Moore J, Smart-Halajko M, Bawazeer N, Al-Daghri NM, McTernan PG, et al.: Vitamin B12 insufficiency induces cholesterol biosynthesis by limiting s-adenosylmethionine and modulating the methylation of SREBF1 and LDLR genes; Clin Epigenetics 7:14; 2015.
3. Agudelo J, Halámková L, Brunelle E, Rodrigues R, Huynh C, Halámek J: Ages at a crime scene: Simultaneous estimation of the time since deposition and age of its originator; Anal Chem 88:6479; 2016.
4. Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten GA, Conneely KN, Warren ST: Age-associated DNA methylation in pediatric populations; Genome Res 22:623; 2012.
5. Anway MD; Cupp A, Uzumcu S, Skinner MK: Epigenetic transgenerational action of endocrine disruptors and male Fertility; Science 308(5727):1466; 2005.
6. Anway MD, Leathers C, Skinner MK: Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease; Endocrinology 147:5515; 2006.
7. Anway MD, Rekow SS, Skinner MK: Transgenerational epigenetic programming of the embryonic testis transcrip- tome; Genomics 91:30; 2008.
8. Aubert G, Lansdorp PM: Telomeres and aging; Physiol Rev 88:557; 2008.
9. Baccino E, Schmitt A: Determination of adult age at death in the forensic context; In Schmitt A, Cunga E, Pinheiro J (Eds): Forensic Anthropology and Medicine: Complementary Sciences from Recovery to Cause of Death; Humana Press: Totiwa, NJ; 2006.
10. Barrès R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O’Gorman DJ, Zierath JR: Acute exercise remodels promoter methylation in human skeletal muscle; Cell Metab 15:405; 2012.
11. Bekaert B, Kamalandua A, Zapico SC, Van De Voorde W, Decorte R: Improved age determination of blood and teeth samples using a selected set of DNA methylation markers; Epigenetics 10:922; 2015.
12. Bell JT, Tsai PC, Yang TP, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, et al.: Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population; PLoS Genet 8(4):e1002629; 2012.
13. Benayoun BA, Pollina EA, Brunet A: Epigenetic regulation of ageing: linking environmental inputs to genomic stability; Nat Rev Mol Cell Biol 16:593; 2015.
14. Bestor TH: The DNA methyltransferases of mammals; Hum Mol Genet 9:2395; 2000.
15. Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL, et al.: High density DNA methylation array with single CpG site resolution; Genomics 98:288; 2011.
16. Bird A: CpG-rich islands and the function of DNA methylation; Nature 321:209; 1986.
17. Bock C, Halbritter F, Carmona FJ, Tierling S, Datlinger P, Assenov Y, Berdasco M, Bergmann AK, Booher K, Busato F, et al.: Quantitative comparison of DNA methylation assays for biomarker development and clinical applications; Nat Biotechnol 34; 2016.
18. Bocklandt S, Lin W, Sehl M, Sánchez F, Sinsheimer J, Horvath S, Vilain E: Epigenetic predictor of age; PLoS One 6(6):e14821; 2011.
19. Boks MP, Derks EM, Weisenberger DJ, Strengman E, Janson E, Sommer IE, Kahn RS, Ophoff RA: The relationship of DNA methylation with age, gender and genotype in twins and healthy controls; PLoS One 4(8):e6767; 2009.
20. Booth LN, Brunet A: The aging epigenome; Mol Cell 62:728; 2016.
21. Booth MJ, Branco MR, Ficz G, Oxley D, Krueger F, Reik W, Balasubramanian S: Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution; Science 336(6083):934; 2012.
22. Børsting C, Morling N: Next generation sequencing and its applications in forensic genetics; Forensic Sci Int Genet 18:78; 2015.
23. Burtner CR, Kennedy BK: Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol 11:567; 2010.
24. Buscarlet M, Tessier A, Provost S, Mollica L, Busque L: Human blood cell levels of 5-hydroxymethylcytosine (5hmC) decline with age, partly related to acquired mutations in TET2; Exp Hematol 44:1072; 2016.
25. Cantone I, Fisher AG: Epigenetic programming and reprogramming during development; Nat Sructural Mol Biol 20:282; 2013.
26. Cavalli G, Paro R: The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis; Cell 93:505; 1998.
27. Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai P, Roetker NS, Just AC, Demerath EW, Guan W, et al.: DNA methylation-based measures of biological age: Meta-analysis predicting time to death; Aging (Albany, NY) 8:1; 2016.
28. Clark SJ, Harrison J, Paul CL, Frommer M: High sensitivity mapping of methylated cytosines; Nucleic Acids Res 22:2990; 1994.
29. Clark SJ, Statham A, Stirzaker C, Molloy PL, Frommer M: DNA methylation: Bisulphite modification and analysis; Nat Protoc 1:2353; 2006.
30. Cotton AM, Price EM, Jones MJ, Balaton BP, Kobor MS, Brown CJ: Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation; Hum Mol Genet 24:1528; 2015.
31. Criscione SW, Zhang Y, Thompson W, Sedivy JM, Neretti N: Transcriptional landscape of repetitive elements in normal and cancer human cells; BMC Genomics 15:583; 2014.
32. Daxinger L, Whitelaw E: Understanding transgenerational epigenetic inheritance via the gametes in mammals; Nat Rev Genet 13:153; 2012.
33. De Tobel J, Hillewig E, Verstraete K: Forensic age estimation based on magnetic resonance imaging of third molars: converting 2D staging into 3D staging; Ann Hum Biol 44:121; 2017.
34. Eckhardt F, Lewin J, Cortese R, Rakyan V, Attwood J, Burger M, Burton J, Cox T, Davies R, Down T, et al.: DNA methylation profiling of human chromosomes 6, 20 and 22; Nat Genet 38:1378; 2006.
35. Eduardoff M, Gross TE, Santos C, De La Puente M, Ballard D, Strobl C, Borsting C, Morling N, Fusco L, Hussing C, et al.: Inter-laboratory evaluation of the EUROFORGEN Global ancestry-informative SNP panel by massively parallel sequencing using the Ion PGM™; Forensic Sci Int Genet 23:178; 2016.
36. Eduardoff M, Santos C, De La Puente M, Gross TE, Fondevila M, Strobl C, Sobrino B, Ballard D, Schneider PM, Carracedo Á, et al.: Inter-laboratory evaluation of SNP-based forensic identification by massively parallel sequencing using the Ion PGM™; Forensic Sci Int Genet 17:110; 2015.
37. Ehrich M, Correll D, van den Boom D: Introduction to EpiTYPER for quantitative DNA methylation analysis using the MassARRAY® System; Sequenom, Inc. (San Diego, CA) Product Preview Note (Doc. no. 8876-007); 2005; https://www.garvan.org.au/research/capabilities/molecular-genetics/documents/introduction-to-dna-methylation-using-the-massarray-system.pdf (accessed June 7, 2017).
38. Eipel M, Mayer F, Arent T, Ferreira MRP, Birkhofer C, Gerstenmaier U, Costa IG, Ritz-Timme S, Wagner W: Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures; Aging (Albany, NY) 8:1034; 2016.
39. Fedoriw AM, Stein P, Svoboda P, Schultz RM, Bartolomei MS: Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting; Science 303(5655):238; 2004.
40. Fernandez A, Assenov Y, Martin-Subero J, Balint B, Siebert R, Taniguchi H, Yamamoto H, Hidalgo M, Tan A, Galm O, et al.: A DNA methylation fingerprint of 1628 human samples; Genome Res 22:407; 2012.
41. Florath I, Butterbach K, Müller H, Bewerunge-hudler M, Brenner H: 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; 2014.
42. Fondevila M, Børsting C, Phillips C, de la Puente MCE, Carracedo A, Morling N, Lareu M: Forensic SNP genotyping with SNaPshot: Technical considerations for the development and optimization of multiplexed SNP assays; Forensic Sci Rev 29:57; 2017.
43. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, et al.: Epigenetic differences arise during the lifetime of monozygotic twins; Proc Natl Acad Sci U S A 102:10604; 2005.
44. Fraser HB, Lam LL, Neumann SM, Kobor MS: Population-specificity of human DNA methylation; Genome Biol 13:R8; 2012.
45. Freire-Aradas A, Phillips C, Mosquera-Miguel A, Girón-Santamaría L, Gómez-Tato A, Casares De Cal M, Álvarez-Dios J, Ansede-Bermejo J, Torres-Español M, Schneider PM, et al.: Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system; Forensic Sci Int Genet 24:65; 2016.
46. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL: A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands; Proc Natl Acad Sci U S A 89:1827; 1992.
47. Garagnani P, Bacalini MG, Pirazzini C, Gori D, Giuliani C, Mari D, Di Blasio AM, Gentilini D, Vitale G, Collino S, et al.: Methylation of ELOVL2 gene as a new epigenetic marker of age; Aging Cell 11:1132; 2012.
48. Gervin K, Andreassen BK, Hjorthaug HS, Carlsen KCL, Carlsen K-H, Undlien DE, Lyle R, Munthe-Kaas MC: Intra-individual changes in DNA methylation not mediated by cell-type composition are correlated with aging during childhood; Clin Epigenetics 8; 2016.
49. Giuliani C, Cilli E, Bacalini MG, Pirazzini C, Sazzini M, Gruppioni G, Franceschi C, Garagnani P, Luiselli D: Inferring chronological age from DNA methylation patterns of human teeth; Am J Phys Anthropol 159:585; 2016.
50. Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A: Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans; Nature 479:365; 2011.
51. Haeusler M, Haas C, Lösch S, Moghaddam N, Villa IM, Walsh S, Kayser M, Seiler R, Ruehli F, Janosa M, et al.: Multidisciplinary identification of the controversial Freedom Fighter Jörg Jenatsch, assassinated 1639 in Chur, Switzerland; PLoS One 11(12):e0168014; 2016.
52. Hagerty SL, Bidwell LC, Harlaar N, Hutchison KE: An exploratory association study of alcohol use disorder and DNA methylation; Alcohol Clin Exp Res 40:1633; 2016.
53. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, et al.: Genomewide methylation profiles reveal quantitative views of human aging rates; Mol Cell 49:359; 2013.
54. Harrell F: Regression Modelling Strategies; Springer-Verlag: New York, NY; 2001.
55. He Y, Ecker JR: Non-CG methylation in the human genome; Annu Rev Genomics Hum Genet 16:55; 2015.
56. Heyn H, Li N, Ferreira HHJ, Moran S, Pisano DG, Gomez A, Diez J: Distinct DNA methylomes of newborns and centenarians; Proc Natl Acad Sci U S A 109:10522; 2012.
57. Heyn H, Moran S, Hernando-herraez I, Res G, Sayols S, Gomez A, Sandoval J, Monk D, Hata K, Marques-bonet T, et al.: DNA methylation contributes to natural human variation DNA methylation contributes to natural human variation; Genome Res 23:1363; 2013.
58. Hofreiter M, Jaenicke V, Serre D, Haeseler A von, Pääbo S: DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA; Nucleic Acids Res 29:4793; 2001.
59. Horvath S: DNA methylation age of human tissues and cell types; Genome Biol 14:R115; 2013.
60. Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D, Di Blasio AM, Giuliani C, Tung S, Vinters H V, et al.: Accelerated epigenetic aging in Down syndrome; Aging Cell 14:491; 2015.
61. Horvath S, Gurven M, Levine ME, Trumble BC, Kaplan H, Allayee H, Ritz BR, Chen B, Lu AT, Rickabaugh TM, et al.: An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease; Genome Biol 17:171; 2016.
62. Horvath S, Levine AJ: HIV-1 infection accelerates age according to the epigenetic clock; J Infect Dis 212:1563; 2015.
63. Horvath S, Pirazzini C, Bacalini MG, Gentilini D, Di Blasio AM, Delledonne M, Mari D, Arosio B, Monti D, Passarino G, et al.: Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring; Aging (Albany, NY) 7:1159; 2015.
64. Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A: The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing; PLoS One 5(1):e8888; 2010.
65. Huang Y, Yan J, Hou J, Fu X, Li L, Hou Y: Developing a DNA methylation assay for human age prediction in blood and bloodstain; Forensic Sci Int Genet 17:129; 2015.
66. Illumina: MethylationEPIC Beadchip; https://www. illumina.com/products/by-type/microarray-kits/infi nium-methylation-epic.html (Accessed May 25, 2017).
67. Illumina: MiSeq.; https://www.illumina.com/technology/next-generation-sequencing/sequencing-technology.html (Accessed May 25, 2017).
68. Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals; Nat Genet 33 Suppl:245; 2003.
69. Jaffe AE, Irizarry RA: Accounting for cellular heterogeneity is critical in epigenome-wide association studies; Genome Biol 15:R31; 2014.
70. Jakobsson A, Westerberg R, Jacobsson A: Fatty acid elongases in mammals: Their regulation and roles in metabolism; Prog Lipid Res 45:237; 2006.
71. Jirtle RL, Skinner MK: Environmental epigenomics and disease susceptibility; Nat Rev Genet 8:253; 2007.
72. Johannessen M, Møler S, Hansen T, Moens U, Van Ghelue M: The multifunctional roles of the four-and-a-half-LIM only protein FHL2; Cell Mol Life Sci 63:268; 2006.
73. Johansson Å, Enroth S, Gyllensten U: Continuous aging of the human DNA methylome throughout the human Lifespan; PLoS One 8(6):e67378; 2013.
74. Jones MJ, Goodman SJ, Kobor MS: DNA methylation and healthy human aging; Aging Cell 14:924; 2015.
75. Jones PA: Functions of DNA methylation: Islands, start sites, gene bodies and beyond; Nat Rev Genet 13:484; 2012.
76. Jung M, Pfeifer GP: Aging and DNA methylation; BMC Biol 13:7; 2015.
77. Kaiser J: The epigenetics heretic; Science 343(6169):361; 2014.
78. Kananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, Kähönen M, Raitakari OT, Hervonen A, Jylhä M, et al.: The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: Evidence from two longitudinal studies; Age (Omaha, NE) 38:65; 2016.
79. Kayser M: Forensic DNA phenotyping: Predicting human appearance from crime scene material for investigative purposes; Forensic Sci Int Genet 18:33; 2015.
80. Koch CM, Wagner W: Epigenetic aging signature to determine age in different tissues; Aging (Albany, NY) 3:1018; 2011.
81. Kriaucionis S, Heintz N: The nuclear DNA base 5-hydroxy-methylcytosine is present in Purkinje neurons and the brain; Science 324(5929):929; 2009.
82. Kudlow BA, Kennedy BK, Monnat RJ: Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases; Nat Rev Mol Cell Biol 8:394; 2007.
83. Laird PW: Principles and challenges of genomewide DNA methylation analysis; Nat Rev Genet 11:191; 2010.
84. Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, et al.: RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer; Cancer Res 66:6512; 2006.
85. Lee HY, Jung SE, Oh YN, Choi A, Yang WI, Shin KJ: Epigenetic age signatures in the forensically relevant body fluid of semen: A preliminary study; Forensic Sci Int Genet 19:28; 2015.
86. Lee JT: Epigenetic regulation by long noncoding RNAs; Science 338(6113):1435; 2012.
87. Lehmann U, Tost J: Pyrosequencing, Methods and Protocols; Humana Press: Clifton, NJ; 2015.
88. Lewis ME, Flavel A: Age assessment of child skeletal remains in forensic contexts; In Schmitt A, Cunha E, Pinheiro J (Eds): Forensic Anthropology and Medicine: Complementary Sciences from Recovery to Cause of Death; Humana Press: Totiwa, NJ; 2006.
89. Li Q, Weidner CI, Costa IG, Marioni RE, Ferreira MR, Deary IJ, Wagner W: DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy; Aging (Albany, NY) 8:394; 2016.
90. Li Y, Tollefsbol TO: Age-related epigenetic drift and phenotypic plasticity loss: Implications in prevention of age-related human diseases; Epigenomics 8:1637; 2016.
91. Lin Q, Wagner W, Zenke M: Analysis of genome-wide DNA methylation profiles by BeadChip technology; Methods Mol Biol 1049:21; 2013.
92. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Nicholas D, Lucero J, Huang Y, Dwork AJ, Schultz MD, et al.: Global epigenomic reconfiguration during mammalian brain development; Science 341(6146):629; 2013.
93. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo Q-M, et al.: Human DNA methylomes at base resolution show widespread epigenomic differences; Nature 462:315; 2009.
94. Liu Q, Jin J, Ying J, Sun M, Cui Y, Zhang L, Xu B, Fan Y, Zhang Q: Frequent epigenetic suppression of tumor suppressor gene glutathione peroxidase 3 by promoter hypermethylation and its clinical implication in clear cell renal cell carcinoma; Int J Mol Sci 16:10636; 2015.
95. Loginov VI, Dmitriev AA, Senchenko VN, Pronina IV, Khodyrev DS, Kudryavtseva AV, Krasnov GS, Gerashchenko GV, Chashchina LI, Kazubskaya TP, et al.: Tumor suppressor function of the SEMA3B gene in human lung and renal cancers; PLoS One 10(5):e0123369; 2015.
96. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G: The hallmarks of aging; Cell 153:1194; 2013.
97. Lucas VS, McDonald F, Andiappan M, Roberts G: Dental age estimation — Root Pulp Visibility (RPV) patterns: A reliable Mandibular Maturity Marker at the 18 year threshold; Forensic Sci Int 270:98; 2017.
98. Man CH, Fung TK, Wan H, Cher CY, Fan A, Ng N, Ho C, Wan TSK, Tanaka T, Wai C, et al.: Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia; Blood 125:3928; 2015.
99. Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, et al.: DNA methylation age of blood predicts all-cause mortality in later life; Genome Biol 16:25; 2015.
100. Márquez-Grant N: An overview of age estimation in forensic anthropology: Perspectives and practical considerations; Ann Hum Biol 42:308; 2015.
101. Martin GM: Epigenetic drift in aging identical twins; Proc Natl Acad Sci U S A 102:10413; 2005.
102. Marttila S, Kananen L, Häyrynen S, Jylhävä J, Nevalainen T, Hervonen A, Jylhä M, Nykter M, Hurme M: Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression; BMC Genomics 16:1; 2015.
103. Matarese F, Carrillo-de Santa Pau E, Stunnenberg HG: 5-Hydroxymethylcytosine: A new kid on the epigenetic block? Mol Syst Biol 7:562; 2011.
104. Mcclay JL, Aberg KA, Clark SL, Nerella S, Kumar G, Xie LY, Hudson AD, Harada A, Hultman CM, Magnusson PKE, et al.: A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects; Hum Mol Genet 23:1175; 2014.
105. Mehta B, Daniel R, Phillips C, Doyle S, Elvidge G, McNevin D: Massively parallel sequencing of customised forensically informative SNP panels on the MiSeq; Electrophoresis 37:2832; 2016.
106. Mehta B, Daniel R, Phillips C, McNevin D: Forensically relevant SNaPshot assays for human DNA SNP analysis: a review; Int J Legal Med 131:21; 2017.
107. Meissner C, Ritz-Timme S: Molecular pathology and age estimation; Forensic Sci Int 203:34; 2010.
108. Meissner C, Von Wurmb N, Schimansky B, Oehmichen M: Estimation of age at death based on quantitation of the 4977-bp deletion of human mitochondrial DNA in skeletal muscle; Forensic Sci Int 105:115; 1999.
109. Moen EL, Zhang X, Mu W, Delaney SM, Wing C, Mcquade J, Myers J, Godley LA, Dolan ME, Zhang W: Genome- wide variation of cytosine modifications between European and African populations and the implications for complex traits; Genetics 194:987; 2013.
110. Moran S, Arribas C, Esteller M: Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences; Epigenomics 8:389; 2016.
111. Morgan HD, Sutherland HG, Martin DI, Whitelaw E: Epigenetic inheritance at the agouti locus in the mouse; Nat Genet 23:314; 1999.
112. Nyrén P: Enzymatic method for continuous monitoring of DNA polymerase activity; Anal Biochem 167:235; 1987.
113. Ohtani S, Yamamoto T: Age estimation by amino acid racemization in human teeth; J Forensic Sci 55:1630; 2010.
114. Okano M, Bell DW, Haber DA, Li E: DNA methyltrans-ferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development; Cell 99:247; 1999.
115. Pabinger S, Ernst K, Pulverer W, Kallmeyer R, Valdes AM, Metrustry S, Katic D, Nuzzo A, Kriegner A, Vierlinger K, et al.: Analysis and visualization tool for targeted amplicon bisulfite sequencing on ion torrent sequencers; PLoS One 11(7):e0160227; 2016.
116. Pal S, Tyler JK: Epigenetics and aging; Sci Adv 2(7): e1600584; 2016.
117. Park JL, Kim JH, Seo E, Bae DH, Kim SY, Lee HC, Woo KM, Kim YS: Identification and evaluation of age-correlated DNA methylation markers for forensic use; Forensic Sci Int Genet 23:64; 2016.
118. Pedersen JS, Valen E, Velazquez AMV, Pedersen JS, Valen E, Velazquez AMV, Parker BJ, Rasmussen M, Lindgreen S, Lilje B, et al.: Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome; Genome Res 24:454; 2014.
119. Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjöström M, Golding J, Alspac T, Team S: Sex-specific, male-line transgenerational responses in humans; Eur J Hum Genet 14:159; 2006.
120. Perna L, Zhang Y, Mons U, Holleczek B, Saum K-U, Brenner H: Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort; Clin Epigenetics 8:64; 2016.
121. Phillips C: Forensic genetic analysis of bio-geographical ancestry; Forensic Sci Int Genet 18:49; 2015.
122. Pidsley R, Zotenko E, Peters TJ, Lawrence MG, Risbridger GP, Molloy P, Van Djik S, Muhlhausler B, Stirzaker C, Clark SJ, et al.: Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling; Genome Biol 17:208; 2016.
123. Pilin A, Pudil F, Bencko V: Changes in colour of different human tissues as a marker of age; Int J Legal Med 121:158; 2007.
124. Rabinowicz PD, Palmer LE, May BP, Hemann MT, Lowe SW, McCombie WR, Martienssen RA: Genes and transposons are differentially methylated in plants, but not in mammals; Genome Res 13:2658; 2003.
125. Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H, Whittaker P, McCann OT, Finer S, Valdes AM, et al.: Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains; Genome Res 20:434; 2010.
126. Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development; Science 293(5532):1089; 2001.
127. Riggs A, Russo V, Martienssen R: Epigenetic mechanisms of gene regulation; Cold Spring Harbor Laboratory Press: Plainview, NY; 1996.
128. Saha A, Wittmeyer J, Cairns BR: Chromatin remodelling: The industrial revolution of DNA around histones; Nat Rev Mol Cell Biol 7:437; 2006.
129. Sakaguchi R, Okamura E, Matsuzaki H, Fukamizu A, Tanimoto K: Sox-Oct motifs contribute to maintenance of the unmethylated H19 ICR in YAC transgenic mice; Hum Mol Genet 22:4627; 2013.
130. Schmeling A, Geserick G, Reisinger W, Olze A: Age estimation; Forensic Sci Int 165:178; 2007.
131. Schmeling A, Dettmeyer R, Rudolf E, Vieth V, Geserick G: Forensic age estimation; Dtsch Ärzteblatt Int 113:44; 2016.
132. Schübeler D: Function and information content of DNA methylation; Nature 517:321; 2015.
133. Simpkin AJ, Howe LD, Tilling K, Gaunt TR, Lyttleton O, McArdle WL, Ring SM, Horvath S, Smith GD, Relton CL: The epigenetic clock and physical development during childhood and adolescence: Longitudinal analysis from a UK birth cohort; Int J Epidemiol (In press); 2017.
134. Skinner MK, Haque CGBM, Nilsson E, Bhandari R, McCarrey JR: Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line; PLoS One 8(7):e66318; 2013.
135. Smith ZD, Meissner A: DNA methylation: Roles in mammalian development; Nat Rev Genet 14:204; 2013.
136. Strahl BD, Allis CD: The language of covalent histone modifications; Nature 403:41; 2000.
137. Suchiman HED, Slieker RC, Kremer D, Slagboom PE, Heijmans BT, Tobi EW: Design, measurement and processing of region-specific DNA methylation assays: The mass spectrometry-based method EpiTYPER; Front Genet 6:1; 2015.
138. Suzuki MM, Bird A: DNA methylation landscapes: Provocative insights from epigenomics; Nat Rev Genet 9:465; 2008.
139. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, et al.: Conversion of 5-methylcytosine to 5-hydroxymethyl-cytosine in mammalian DNA by MLL partner TET1; Science 324(5929):930; 2009.
140. Talens RP, Christensen K, Putter H, Willemsen G, Christiansen L, Kremer D, Suchiman HED, Slagboom PE, Boomsma DI, Heijmans BT: Epigenetic variation during the adult lifespan: Cross-sectional and longitudinal data on monozygotic twin pairs; Aging Cell 11:694; 2012.
141. Tan H, Qurashi A, Poidevin M, Nelson DL, Li H, Jin P: Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration; Hum Mol Genet 21:57; 2012.
142. Tan Q, Heijmans BT, Hjelmborg JvB, Soerensen M, Christensen K, Christiansen L: Epigenetic drift in the aging genome: A ten-year follow-up in an elderly twin cohort; Int J Epidemiol 45:1146; 2016.
143. ThermoFischer: Ion Torrent PGM; https://www. thermofi sher.com/de/de/home/life-science/sequencing/next-generation-sequencing/ion-torrent-next-generation-sequencing-technology.html(Accessed May 25, 2017).
144. Tiffen J, Wilson S, Gallagher SJ, Hersey P, Filipp FV: Somatic copy number amplification and hyperactivating somatic mutations of EZH2 correlate with DNA methylation and drive epigenetic silencing of genes involved in tumor suppression and immune responses in melanoma; Neoplasia 18:121; 2016.
145. Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K, Kelsey G, Sasaki H: Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes; Development 138:811; 2011.
146. Tost J, Gut IG: DNA methylation analysis by pyrose-quencing; Nat Protoc 2:2265; 2007.
147. Tsaprouni LG, Yang TP, Bell J, Dick KJ, Kanoni S, Nisbet J, Viñuela A, Grundberg E, Nelson CP, Meduri E, et al.: Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation; Epigenetics 9:1382; 2014.
148. Turelli P, Castro-diaz N, Marzetta F, Kapopoulou A, Duc J, Tieng V, Quenneville S, Trono D: Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements; Genome Res 24:1260; 2014.
149. Turner BM: Defining an epigenetic code; Nat Cell Biol 9:2; 2007.
150. Urdinguio RG, Torró MI, Bayón GF, Álvarez-Pitti J, Fernández AF, Redon P, Fraga MF, Lurbe E: Longitudinal study of DNA methylation during the first 5 years of life; J Transl Med 14:160; 2016.
151. Vaca-Paniagua F, Oliver J, Nogueira da Costa A, Merle P, McKay J, Herceg Z, Holmila R: Targeted deep DNA methylation analysis of circulating cell-free DNA in plasma using massively parallel semiconductor sequencing; Epigenomics 7:353; 2015.
152. van Dongen J, Nivard MG, Willemsen G, Hottenga J-J, Helmer Q, Dolan CV, Ehli EA, Davies GE, van Iterson M, Breeze CE, et al.: Genetic and environmental influences interact with age and sex in shaping the human methylome; Nat Commun 7:11115; 2016.
153. Vidaki A, Ballard D, Aliferi A, Miller TH, Barron LP, Syndercombe Court D: DNA methylation-based forensic age prediction using artificial neural networks and next generation sequencing; Forensic Sci Int Genet 28:225; 2017.
154. Vidaki A, Daniel B, Syndercombe Court D: Forensic DNA methylation profiling — Potential opportunities and challenges; Forensic Sci Int Genet 7:499; 2013.
155. Walker RF, Liu JS, Peters BA, Ritz BR, Wu T, Ophoff RA, Horvath S: Epigenetic age analysis of children who seem to evade aging; Aging (Albany, NY) 7:334; 2015.
156. Weidner CI, Lin Q, Koch CM, Eisele L, Beier F, Ziegler P, Bauerschlag DO, Jöckel K-H, Erbel R, Mühleisen TW, et al.: Aging of blood can be tracked by DNA methylation changes at just three CpG sites; Genome Biol 15:R24; 2014.
157. Wright K, Mundorff A, Chaseling J, Forrest A, Maguire C, Crane DI: A new disaster victim identification management strategy targeting “near identification-threshold” cases: Experiences from the Boxing Day tsunami; Forensic Sci Int 250:91; 2015.
158. Xu C-J, Bonder MJ, Söderhäll C, Bustamante M, Baïz N, Gehring U, Jankipersadsing SA, van der Vlies P, van Diemen CC, van Rijkom B, et al.: The emerging landscape of dynamic DNA methylation in early childhood; BMC Genomics 18:25; 2017.
159. Xu C, Qu H, Wang G, Xie B, Shi Y, Yang Y, Zhao Z, Hu L, Fang X, Yan J, et al.: A novel strategy for forensic age prediction by DNA methylation and support vector regression model; Sci Rep 5:17788; 2015.
160. Yang Y, Hu JF, Ulaner GA, Li T, Yao X, Vu TH, Hoffman AR: Epigenetic regulation of Igf2/H19 imprinting at CTCF insulator binding sites; J Cell Biochem 90:1038; 2003.
161. Yu M, Hon GC, Szulwach KE, Song C-X, Jin P, Ren B, He C: Tet-assisted bisulfite sequencing of 5-hydroxymethyl-cytosine; Nat Protoc 7:2159; 2012.
162. Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Bürkle A, Caiafa P: Reconfiguration of DNA methylation in aging; Mech Ageing Dev 151:60; 2015.
163. Zbieć-Piekarska R, Spólnicka M, Kupiec T, Makowska Z, Spas A, Parys-Proszek A, Kucharczyk K, Płoski R, Branicki W: 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; 2015.
164. Zbieć-Piekarska R, Spólnicka M, Kupiec T, Parys-Proszek A, Makowska Z, Pałeczka A, Kucharczyk K, Płoski R, Branicki W: Development of a forensically useful age prediction method based on DNA methylation analysis; Forensic Sci Int Genet 17:173; 2015.
165. Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT-Y, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE, et al.: Charting a dynamic DNA methylation landscape of the human genome; Nature 500:477; 2013.
166. Ziller MJ, Stamenova EK, Gu H, Gnirke A, Meissner A: Targeted bisulfite sequencing of the dynamic DNA methylome; Epigenetics Chromatin 9:55; 2016.
167. Zubakov D, Liu F, Kokmeijer I, Choi Y, van Meurs JBJ, van IJcken WFJ, Uitterlinden AG, Hofman A, Broer L, van Duijn CM, et al.: Human age estimation from blood using mRNA, DNA methylation, DNA rearrangement, and telomere length; Forensic Sci Int Genet 24:33; 2016.
168. Zubakov D, Liu F, Van Zelm MC, Vermeulen J, Oostra BA, Van Duijn CM, Driessen GJ, Van Dongen JJM, Kayser M, Langerak AW: Estimating human age from T-cell DNA rearrangements; Curr Biol 20:R970; 2010.