Abstract
BackgroundThe change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases. However, the course of variation in methylation levels with age, the difference in methylation between genders, and methylation-disease association at the whole genome level is unclear. In the present study, genome-wide methylation levels in DNA extracted from peripheral blood for 2116 healthy Chinese in the 2–97 age range and 280 autistic trios were examined using the fluorescence polarization-based genome-wide DNA methylation quantification method developed by us.ResultsGenome-wide or global DNA methylation levels proceeded through multiple phases of variation with age, consisting of a steady increase from age 2 to 25 (r = 0.382) and another rise from age 41 to 55 to reach a peak level of ~80 % (r = 0.265), followed by a sharp decrease to ~40 % in the mid-1970s (age 56 to 75; r = −0.395) and leveling off thereafter. Significant gender effect in methylation levels was observed only for the 41–55 age group in which methylation in females was significantly higher than in males (p = 0.010). In addition, global methylation level was significantly higher in autistic children than in age-matched healthy children (p < 0.001).ConclusionsThe multiphasic nature of changes in global methylation levels with age was delineated, and investigation into the factors underlying this profile will be essential to a proper understanding of the aging process. Furthermore, this first report of global hypermethylation in autistic children also illustrates the importance of age-matched controls in characterization of disease-associated variations in DNA methylation.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-016-0086-y) contains supplementary material, which is available to authorized users.
Highlights
The change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases
DNA methylation is the most common epigenetic modification that plays an essential role in the regulation of tissue-specific gene expression, cellular differentiation, chromosome stabilization, genomic imprinting
In particular DNA methylation, have been reported to occur in normal physiological development and aging, and alterations in DNA methylation associated with the signaling and regulation of transcription have been demonstrated in some genes [7, 8]
Summary
The change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases. DNA methylation is the most common epigenetic modification that plays an essential role in the regulation of tissue-specific gene expression, cellular differentiation, chromosome stabilization, genomic imprinting, Changes in epigenetics signatures, and in particular DNA methylation, have been reported to occur in normal physiological development and aging, and alterations in DNA methylation associated with the signaling and regulation of transcription have been demonstrated in some genes [7, 8]. Various HPLC-based, sequencing-based, (e.g., bisulfite-sequencing and methylated DNA immunoprecipitation) and microarray-based methods have been introduced to quantitate genomic DNA methylation [12]. These methods enable high-resolution and detailed methylation profiles of individual genes, they are time-consuming and incapable of measuring whole genome methylation levels accurately. A number of methods have been developed to render possible the measurement of whole genome methylation levels, including the LUminometric Methylation Assay (LUMA) method [13], the ELISA-based approach [14], and the fluorescence polarization DNA methylation (FPDM) method developed by us [15]
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