Skip to main content
Top
Published in: International Journal of Legal Medicine 1/2018

Open Access 01-01-2018 | Original Article

DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups

Authors: M. Spólnicka, E. Pośpiech, B. Pepłońska, R. Zbieć-Piekarska, Ż. Makowska, A. Pięta, J. Karłowska-Pik, B. Ziemkiewicz, M. Wężyk, P. Gasperowicz, T. Bednarczuk, M. Barcikowska, C. Żekanowski, R. Płoski, Wojciech Branicki

Published in: International Journal of Legal Medicine | Issue 1/2018

Login to get access

Abstract

Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer’s disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for TRIM59 and KLF14 markers in the group of early onset Alzheimer’s disease suggesting accelerated aging of patients. In the Graves’ disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for TRIM59 and FHL2 with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the ELOVL2 and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses.
Literature
1.
go back to reference Kayser M (2015) Forensic DNA phenotyping: predicting human appearance from crime scene material for investigative purposes. Forensic Sci Int Genet 18:33–48PubMed Kayser M (2015) Forensic DNA phenotyping: predicting human appearance from crime scene material for investigative purposes. Forensic Sci Int Genet 18:33–48PubMed
3.
4.
go back to reference Bekaert B, Kamalandua A, Zapico SC et al (2015) Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. Epigenetics 10:922–930PubMedPubMedCentral Bekaert B, Kamalandua A, Zapico SC et al (2015) Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. Epigenetics 10:922–930PubMedPubMedCentral
5.
go back to reference Visser M, Kayser M, Palstra RJ (2012) HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res 22:446–455PubMedPubMedCentral Visser M, Kayser M, Palstra RJ (2012) HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res 22:446–455PubMedPubMedCentral
6.
go back to reference Santos C, Phillips C, Fondevila M et al (2016) Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region. Forensic Sci Int Genet 20:71–80PubMed Santos C, Phillips C, Fondevila M et al (2016) Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region. Forensic Sci Int Genet 20:71–80PubMed
8.
go back to reference Hannum G, Guinney J, Zhao L et al (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49:359–376PubMed Hannum G, Guinney J, Zhao L et al (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49:359–376PubMed
9.
go back to reference Johansson A, Enroth S, Gyllensten U (2013) Continuous aging of the human DNA methylome throughout the human lifespan. PLoS One 8:e67378PubMedPubMedCentral Johansson A, Enroth S, Gyllensten U (2013) Continuous aging of the human DNA methylome throughout the human lifespan. PLoS One 8:e67378PubMedPubMedCentral
10.
go back to reference Weidner CI, Lin Q, Koch CM et al (2014) Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 15:R24PubMedPubMedCentral Weidner CI, Lin Q, Koch CM et al (2014) Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 15:R24PubMedPubMedCentral
13.
go back to reference Freire-Aradas A, Phillips C, Mosquera-Miguel A et al (2016) 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 24:65–74. doi:10.1016/j.fsigen.2016.06.005 PubMed Freire-Aradas A, Phillips C, Mosquera-Miguel A et al (2016) 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 24:65–74. doi:10.​1016/​j.​fsigen.​2016.​06.​005 PubMed
16.
go back to reference Marioni RE, Shah S, McRae AF et al (2015) The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol 44:1388–1396PubMedPubMedCentral Marioni RE, Shah S, McRae AF et al (2015) The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol 44:1388–1396PubMedPubMedCentral
17.
go back to reference Bacalini MG, Deelen J, Pirazzini C et al (2016) Systemic age-associated DNA hypermethylation of ELOVL2 gene: in vivo and in vitro evidences of a cell replication process. J Gerontol A Biol Sci Med Sci. doi:10.1093/gerona/glw185 Bacalini MG, Deelen J, Pirazzini C et al (2016) Systemic age-associated DNA hypermethylation of ELOVL2 gene: in vivo and in vitro evidences of a cell replication process. J Gerontol A Biol Sci Med Sci. doi:10.​1093/​gerona/​glw185
18.
go back to reference Miller SA et al (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedPubMedCentral Miller SA et al (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedPubMedCentral
19.
go back to reference Köchl S, Niederstätter H, Parson W (2005) DNA extraction and quantitation of forensic samples using the phenol-chloroform method and real-time PCR. Methods Mol Biol 297:13–30PubMed Köchl S, Niederstätter H, Parson W (2005) DNA extraction and quantitation of forensic samples using the phenol-chloroform method and real-time PCR. Methods Mol Biol 297:13–30PubMed
20.
go back to reference Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350:1191–1193PubMedPubMedCentral Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350:1191–1193PubMedPubMedCentral
21.
go back to reference Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22:R741–R752PubMed Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22:R741–R752PubMed
22.
go back to reference Moore BD, Chakrabarty P, Levites Y et al (2012) Overlapping profiles of Aβ peptides in the Alzheimer’s disease and pathological aging brains. Alzheimers Res Ther 4:18PubMedPubMedCentral Moore BD, Chakrabarty P, Levites Y et al (2012) Overlapping profiles of Aβ peptides in the Alzheimer’s disease and pathological aging brains. Alzheimers Res Ther 4:18PubMedPubMedCentral
23.
go back to reference Zekanowski C, Styczyńska M, Pepłońska B et al (2003) Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol 184:991–996PubMed Zekanowski C, Styczyńska M, Pepłońska B et al (2003) Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol 184:991–996PubMed
24.
go back to reference Zekanowski C, Religa D, Safranow K et al (2005) The -22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer's disease in Poland. J Neural Transm 112:839–845PubMed Zekanowski C, Religa D, Safranow K et al (2005) The -22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer's disease in Poland. J Neural Transm 112:839–845PubMed
25.
go back to reference Bialopiotrowicz E, Kuzniewska B, Kachamakova-Trojanowska N et al (2011) Cell cycle regulation distinguishes lymphocytes from sporadic and familial Alzheimer’s disease patients. Neurobiol Aging 32:2319.e13–2319.e26. doi:10.1016/j.neurobiolaging.2010.04.017 Bialopiotrowicz E, Kuzniewska B, Kachamakova-Trojanowska N et al (2011) Cell cycle regulation distinguishes lymphocytes from sporadic and familial Alzheimer’s disease patients. Neurobiol Aging 32:2319.e13–2319.e26. doi:10.​1016/​j.​neurobiolaging.​2010.​04.​017
26.
go back to reference Cuyvers E, Sleegers K (2016) Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond. Lancet Neurol 15:857–868PubMed Cuyvers E, Sleegers K (2016) Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond. Lancet Neurol 15:857–868PubMed
27.
go back to reference Sanchez-Mut JV, Heyn H, Vidal E et al (2016) Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl Psychiatry 6:e718PubMedPubMedCentral Sanchez-Mut JV, Heyn H, Vidal E et al (2016) Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl Psychiatry 6:e718PubMedPubMedCentral
28.
29.
go back to reference Tannorella P, Stoccoro A, Tognoni G et al (2015) Methylation analysis of multiple genes in blood DNA of Alzheimer’s disease and healthy individuals. Neurosci Lett 600:143–147PubMed Tannorella P, Stoccoro A, Tognoni G et al (2015) Methylation analysis of multiple genes in blood DNA of Alzheimer’s disease and healthy individuals. Neurosci Lett 600:143–147PubMed
30.
go back to reference Di Francesco A, Arosio B, Falconi A et al (2015) Global changes in DNA methylation in Alzheimer’s disease peripheral blood mononuclear cells. Brain Behav Immun 45:139–144PubMed Di Francesco A, Arosio B, Falconi A et al (2015) Global changes in DNA methylation in Alzheimer’s disease peripheral blood mononuclear cells. Brain Behav Immun 45:139–144PubMed
31.
32.
go back to reference Strawa K, Markowska A, Miśkiewicz P et al (2014) Increased concentration of T-cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves’ disease. Clin Endocrinol 81:769–774 Strawa K, Markowska A, Miśkiewicz P et al (2014) Increased concentration of T-cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves’ disease. Clin Endocrinol 81:769–774
33.
go back to reference Zubakov D, Liu F, VanZelm MC et al (2010) Estimating human age from T-cell DNA rearrangements. Curr Biol 20:R970–R971PubMed Zubakov D, Liu F, VanZelm MC et al (2010) Estimating human age from T-cell DNA rearrangements. Curr Biol 20:R970–R971PubMed
34.
go back to reference Kadrmas JL, Beckerle MC (2004) The LIM domain: from the cytoskeleton to the nucleus. Nat Rev Mol Cell Biol 5:920–931PubMed Kadrmas JL, Beckerle MC (2004) The LIM domain: from the cytoskeleton to the nucleus. Nat Rev Mol Cell Biol 5:920–931PubMed
35.
go back to reference Verset L, Feys L, Trépant AL (2016) FHL2: a scaffold protein of carcinogenesis, tumour-stroma interactions and treatment response. Histol Histopathol 31:469–478PubMed Verset L, Feys L, Trépant AL (2016) FHL2: a scaffold protein of carcinogenesis, tumour-stroma interactions and treatment response. Histol Histopathol 31:469–478PubMed
36.
go back to reference WangJ YY, Xia HH et al (2007) Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis. Gastroenterology 132:1066–1076 WangJ YY, Xia HH et al (2007) Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis. Gastroenterology 132:1066–1076
37.
go back to reference Amann T, Egle Y, Bosserhoff AK et al (2010) FHL2 suppresses growth and differentiation of the colon cancer cell line HT-29. Oncol Rep 23:1669–1674PubMed Amann T, Egle Y, Bosserhoff AK et al (2010) FHL2 suppresses growth and differentiation of the colon cancer cell line HT-29. Oncol Rep 23:1669–1674PubMed
38.
go back to reference McCarthy (2005) Involvement of presenilins in cell-survival signalling pathways. Biochem Soc Trans33:568–572 McCarthy (2005) Involvement of presenilins in cell-survival signalling pathways. Biochem Soc Trans33:568–572
39.
go back to reference Tanahashi H, Tabira T et al (2000) Alzheimer’s disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein. Hum Mol Genet 9:2281–2289PubMed Tanahashi H, Tabira T et al (2000) Alzheimer’s disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein. Hum Mol Genet 9:2281–2289PubMed
41.
go back to reference Balastik M, Ferraguti F, Pires-da Silva A et al (2008) Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration. Proc Natl Acad Sci U S A 105:12016–12021PubMedPubMedCentral Balastik M, Ferraguti F, Pires-da Silva A et al (2008) Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration. Proc Natl Acad Sci U S A 105:12016–12021PubMedPubMedCentral
43.
44.
go back to reference Seo S, Lomberk G, Mathison A et al (2012) Krüppel-like factor 11 differentially couples to histone acetyltransferase and histone methyltransferase chromatin remodeling pathways to transcriptionally regulate dopamine D2 receptor in neuronal cells. J Biol Chem 287:12723–12735. doi:10.1074/jbc.M112.351395 PubMedPubMedCentral Seo S, Lomberk G, Mathison A et al (2012) Krüppel-like factor 11 differentially couples to histone acetyltransferase and histone methyltransferase chromatin remodeling pathways to transcriptionally regulate dopamine D2 receptor in neuronal cells. J Biol Chem 287:12723–12735. doi:10.​1074/​jbc.​M112.​351395 PubMedPubMedCentral
45.
46.
go back to reference Gervin K, Andreassen BK, Hjorthaug HS et al (2016) Intra-individual changes in DNA methylation not mediated by cell-type composition are correlated with aging during childhood. Clin Epigenetics 8:110PubMedPubMedCentral Gervin K, Andreassen BK, Hjorthaug HS et al (2016) Intra-individual changes in DNA methylation not mediated by cell-type composition are correlated with aging during childhood. Clin Epigenetics 8:110PubMedPubMedCentral
47.
48.
go back to reference Weidner CI, Ziegler P, Hahn M et al (2015) Epigenetic aging upon allogeneic transplantation: the hematopoietic niche does not affect age-associated DNA methylation. Leukemia 29:985–988. doi:10.1038/leu.2014.323 PubMed Weidner CI, Ziegler P, Hahn M et al (2015) Epigenetic aging upon allogeneic transplantation: the hematopoietic niche does not affect age-associated DNA methylation. Leukemia 29:985–988. doi:10.​1038/​leu.​2014.​323 PubMed
50.
go back to reference Smith TJ, Hegedüs L (2016) Graves’ disease. N Engl J Med 375:1552–1565PubMed Smith TJ, Hegedüs L (2016) Graves’ disease. N Engl J Med 375:1552–1565PubMed
51.
go back to reference Garagnani P, Bacalini MG, Pirazzini C (2012) Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 11:1132–1134PubMed Garagnani P, Bacalini MG, Pirazzini C (2012) Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 11:1132–1134PubMed
54.
go back to reference Rojas R (1996) Neural networks: a systematicintroduction. Springer, Berlin Rojas R (1996) Neural networks: a systematicintroduction. Springer, Berlin
55.
go back to reference Tu JV (1996) Advantages and disadvantages of using artificial neural networks versus logistic regression for predicting medical outcomes. J Clin Epidemid 49:1225–1231 Tu JV (1996) Advantages and disadvantages of using artificial neural networks versus logistic regression for predicting medical outcomes. J Clin Epidemid 49:1225–1231
56.
go back to reference Basheer IA, Hajmeer M (2000) Artificial neural networks: fundamentals, computing, design, and application. J Microbiol Methods 43:3–31PubMed Basheer IA, Hajmeer M (2000) Artificial neural networks: fundamentals, computing, design, and application. J Microbiol Methods 43:3–31PubMed
57.
go back to reference Amato F, López A, Peña-Méndez EM et al (2013) Artificial neural networks in medical diagnosis. J Appl Biomed 11:47–58 Amato F, López A, Peña-Méndez EM et al (2013) Artificial neural networks in medical diagnosis. J Appl Biomed 11:47–58
59.
go back to reference 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. doi:10.1016/j.fsigen.2017.02.009 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. doi:10.​1016/​j.​fsigen.​2017.​02.​009
Metadata
Title
DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups
Authors
M. Spólnicka
E. Pośpiech
B. Pepłońska
R. Zbieć-Piekarska
Ż. Makowska
A. Pięta
J. Karłowska-Pik
B. Ziemkiewicz
M. Wężyk
P. Gasperowicz
T. Bednarczuk
M. Barcikowska
C. Żekanowski
R. Płoski
Wojciech Branicki
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Legal Medicine / Issue 1/2018
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-017-1636-0

Other articles of this Issue 1/2018

International Journal of Legal Medicine 1/2018 Go to the issue