Variation of global DNA methylation levels with age and in autistic children

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.

Forward and reverse mutations in stages of cancer development

“…Furthermore, these two groups of SNVs declined with the age at diagnosis (Fig. 2e ), in resemblance to the decrease of global DNA methylation in old age [ 43 ]. The correlation between somatic CNVs with CpGe and MeMRE (Fig.…”

DNA Methylation and Susceptibility to Autism Spectrum Disorder

“…Genome-wide DNA methylation profiling in ASD patients is considered an ideal experimental approach to identify candidate loci with abnormal methylation. However, due to the limited availability of brain tissues, many studies have used blood samples to investigate 5mC in ASD (63, 78, 79). Interestingly, the genome-wide methylation pattern in sperm DNA has been associated with early signs of ASD risk in one ASD cohort (80).…”

Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes

“…Although a single ultimate neuropathological feature in the brains of individuals with ASD may be impossible to define, we now know that common variant of small effect and rare de novo variants of large effect can combine to influence the risk for ASD. Apart from de novo mutations, copy number variations 13 – 15 , and aberrant microRNA profiles 16 , epigenetic mechanisms such as variations in DNA methylation on differential gene expression have been proposed to play a pivotal role in ASD 17 – 19 . Although Fragile X syndrome is the most well-known single-gene disorder, it only accounts for approximately 5% of all ASD cases 20 ; the cause of most cases of ASD are unclear.…”