Sex-related differences in acquired gene expression clarified
Achievements by Japan’s first twin research center
DNA methylation is a typical DNA modification involved in epigenetic control of gene expression and is drawing attention as an acquired factor affecting disease development. It is expected that DNA modification will influence clinical examinations and treatment in the future. Since individual differences in the sensitivity to DNA methylation were not clarified and there was also a possibility that the sensitivity to DNA methylation might be genetically determined, it was hard to examine individuals with different genes, such as humans.
A research group led by Associate Professor WATANABE Mikio and Professor IWATANI Yoshinori at the Center for Twin Research, Graduate School of Medicine, Osaka University, examined individual differences in DNA methylation levels in identical twins. By eliminating genetic factors, they analyzed individual differences in DNA methylation levels through comparison with identical DNA sequences.
As a result, this group clarified for the first time that individual differences in most autosomal methylation levels were greater in men than women whereas those in the X chromosome were greater in women. This was achieved because the Center for Twin Research is the only research center in Japan that systematically collects samples of identical twins.
It is expected that this group’s achievement will become basic data for using DNA methylation for clinical examinations and treatment and will contribute to the clarification of DNA methylation’s effects on sex-related individual differences in disease development and clinical progression. Furthermore, the possibility of higher susceptibility of men to acquired factors (environmental factors) was also suggested.
This group’s achievement provided basic data essential for clinical examinations and treatment using DNA methylation, which will lead to the clarification of DNA methylation’s effects on diseases with sex-related individual differences in the incidence of disease and clinical course.
Fig. 1: Differences in the within-pair differences of methylation levels of autosomal Chromosome in identical twins are larger in male than female pairs. (Those of X-chromosome are larger in female pairs)
DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic analysis of DNA methylation in monozygotic twins, an optimal model to evaluate them because the genetic backgrounds are the same.
We examined 30 male and 43 female older monozygotic twin pairs recruited from the registry established by the Center for Twin Research, Osaka University. Their methylation levels were determined using the Infinium HumanMethylation450 BeadChip Kit (Illumina), which interrogated 485577 highly informative CpG sites at the single-nucleotide resolution, and the median methylation level was calculated for each of the 25657 CpG islands. Within-pair differences of methylation levels (WPDMs) were greater in male pairs than female pairs for 86.0 % of autosomal CpG islands, but were higher in female pairs than male pairs for 76.7 % of X chromosomal CpG islands. Mean WPDMs of CpG islands in each autosomal chromosome were significantly higher in male pairs than in female whereas that in X chromosome was significantly higher in female pairs than in male. Multiple comparison indicated that WPDMs in three autosomal and two X-chromosomal CpG islands were significantly greater in male pairs, whereas those in 22 X-chromosomal CpG islands were significantly greater in female pairs.
Sex-related differences were present in the WPDMs of CpG islands in individuals with the same genetic background. These differences may be associated with the sexual influences in susceptibility of some diseases.
To learn more about this research, please view the full research report entitled “ Within-pair Differences of DNA Methylation Levels between Monozygotic Twins are Different between Male and Female pairs ” at this page of the BMC Medical Genomics website.