EDARADD
Ectodysplasin-A receptor-associated adapter protein (EDAR-associated death domain protein) (Protein crinkled homolog)
Publications[править]
DNA methylation analysis in a variety of genes has brought promising results in age estimation. The main aim of this study was to evaluate DNA methylation levels from four age-correlated genes, ELOVL2, FHL2, EDARADD and PDE4C, in blood samples of healthy Portuguese individuals. Fifty-three samples were analyzed through the bisulfite polymerase chain reaction (PCR) sequencing method for CpG dinucleotide methylation status. Linear regression models were used to analyze relationships between methylation levels and chronological age. The highest age-associated CpG in each locus was chosen to build a multi-locus age prediction model (APM), allowing to obtain a Mean Absolute Deviation (MAD) between chronological and predicted ages of 5.35 years, explaining 94.1% of age variation. Validation approaches demonstrated the accuracy and reproducibility of the proposed multi-locus APM. Testing the APM in 51 blood samples from deceased individuals a MAD of 9.72 years was obtained. Potential differences in methylation status between samples from living and deceased individuals could exist since the highest age-correlated CpGs were different in some genes between both groups. In conclusion, our study using the bisulfite PCR sequencing method is in accordance with the high age prediction accuracy of DNA methylation levels in four previously reported age-associated genes. DNA methylation pattern differences between blood samples from living and deceased individuals should be taken into account in forensic contexts.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Child
- Child, Preschool
- CpG Islands
- Cyclic Nucleotide Phosphodiesterases, Type 4
- DNA Methylation
- Edar-Associated Death Domain Protein
- Fatty Acid Elongases
- Female
- Forensic Genetics
- Humans
- Infant
- LIM-Homeodomain Proteins
- Male
- Middle Aged
- Muscle Proteins
- Polymerase Chain Reaction
- Transcription Factors
- Young Adult
Keywords
- Age the living
- CpGs
- DNA methylation age
- Forensic epigenetics
- Forensic sciences
Age estimation using DNA methylation levels has been widely investigated in recent years because of its potential application in forensic genetics. The main aim of this study was to develop an age predictor model (APM) for blood samples of deceased individuals based in five age-correlated genes. Fifty-one samples were analyzed through the bisulfite polymerase chain reaction (PCR) sequencing method for DNA methylation evaluation in genes ELOVL2, FHL2, EDARADD, PDE4C, and C1orf132. Linear regression was used to analyze relationships between methylation levels and age. The model using the highest age-correlated CpG from each locus revealed a correlation coefficient of 0.888, explaining 76.3% of age variation, with a mean absolute deviation from the chronological age (MAD) of 6.08 years. The model was validated in an independent test set of 19 samples producing a MAD of 8.84 years. The developed APM seems to be informative and could have potential application in forensic analysis.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- CpG Islands
- Cyclic Nucleotide Phosphodiesterases, Type 4
- DNA Methylation
- Edar-Associated Death Domain Protein
- Fatty Acid Elongases
- Female
- Forensic Genetics
- Genetic Markers
- Humans
- LIM-Homeodomain Proteins
- Linear Models
- Male
- Middle Aged
- Muscle Proteins
- Polymerase Chain Reaction
- Sequence Analysis, DNA
- Sulfites
- Transcription Factors
- Young Adult
Keywords
- DNA methylation age
- bisulfite PCR sequencing
- deceased individuals
- forensic epigenetics
- forensic science
Most seabirds do not have any outward identifiers of their chronological age, so estimation of seabird population age structure generally requires expensive, long-term banding studies. We investigated the potential to use a molecular age biomarker to estimate age in short-tailed shearwaters (Ardenna tenuirostris). We quantified DNA methylation in several A. tenuirostris genes that have shown age-related methylation changes in mammals. In birds ranging from chicks to 21 years of age, bisulphite treated blood and feather DNA was sequenced and methylation levels analysed in 67 CpG sites in 13 target gene regions. From blood samples, five of the top relationships with age were identified in KCNC3 loci (CpG66: R2 = 0.325, p = 0.019). In feather samples ELOVL2 (CpG42: R2 = 0.285, p = 0.00048) and EDARADD (CpG46: R2 = 0.168, p = 0.0067) were also weakly correlated with age. However, the majority of markers had no clear association with age (of 131 comparisons only 12 had a p-value < 0.05) and statistical analysis using a penalised lasso approach did not produce an accurate ageing model. Our data indicate that some age-related signatures identified in orthologous mammalian genes are not conserved in the long-lived short tailed shearwater. Alternative molecular approaches will be required to identify a reliable biomarker of chronological age in these seabirds.
MeSH Terms
- Aging
- Animals
- Base Sequence
- Birds
- DNA Methylation
- Gene Amplification
- Mammals
- Sequence Analysis, DNA
- Sequence Homology, Nucleic Acid
From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age in saliva of 34 male identical twin pairs between 21 and 55 years of age. Furthermore, we validated sites in the promoters of three genes and replicated our results in a general population sample of 31 males and 29 females between 18 and 70 years of age. The methylation of three sites--in the promoters of the EDARADD, TOM1L1, and NPTX2 genes--is linear with age over a range of five decades. Using just two cytosines from these loci, we built a regression model that explained 73% of the variance in age, and is able to predict the age of an individual with an average accuracy of 5.2 years. In forensic science, such a model could estimate the age of a person, based on a biological sample alone. Furthermore, a measurement of relevant sites in the genome could be a tool in routine medical screening to predict the risk of age-related diseases and to tailor interventions based on the epigenetic bio-age instead of the chronological age.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- DNA Methylation
- DNA Probes
- Epigenesis, Genetic
- Female
- Genetic Loci
- Humans
- Male
- Middle Aged
- Models, Genetic
- Oligonucleotide Array Sequence Analysis
- Reproducibility of Results
- Saliva
- Twins
- Young Adult