Mules are well known for being stubborn creatures, but they aren’t alone. It seems that resistance to change is something they may have in common with body weight and certain stretches of your epigenome. Andrew Feinberg and M. Daniele Fallin at Johns Hopkins University led several teams in a study that shows, for the first time, that an individual’s DNA methylation patterns in some spots can remain static for years.
The investigators obtained samples from the AGES study, part of the 1967 Reykjavik Study of 18,000 Icelanders. In 2002, the AGES study recruited 5758 of the surviving participants of which 638 had provided a DNA samples in 1991, giving the investigators two sets of DNA from the same individuals, taken 11 years apart.
The group randomly chose genomes of 74 individuals from this set for a genome-wide CHARM analysis of CpG sites. They identified 227 variably methylated regions (VMRs) which tended to be located around developmental genes. About half of the VMRs looked the same both in 1991 and in 2002 and could be used to identify individuals, much like an epigenetic “fingerprint”. This discovery is interesting because some experts have argued that DNA methylation changes over time due to environmental effects, while others think methylation patterns are inherited and not dynamic. This study shows both can simultaneously occur.
But Fallin cautions, “We looked at changes over a decade among elderly participants. So, while there was a subset of VMRs that were stable over that decade, we cannot tell whether these sites were modifiable much earlier in life or whether a person’s methylation status at these stable VMRs was indeed inherited and thus constant throughout their life. This is an important follow-up question.”
The group next explored how methylation of particular VMRs played into disease risk. They looked for correlations with the body mass index (BMI), which has been associated with several diseases. Among the stable VMRs, they found 13 genes, of which 4 correlated with BMI in both the 1991 and 2002 sample sets. The remaining genes had links to obesity and diabetes. To see how much of that beer belly you can chalk up to static DNA methylation, check out Science Translation Medicine, September 2010