Study of how genome is chemically altered as we age could help us
understand disease.
Different families have different 'styles' of lifelong DNA change.Getty
The chemical markers on people's DNA change throughout their life, an
international team of researchers has found.
And the way they change - that is, whether markers are gained or lost -
runs in the family, showing that these 'epigenetic' features, although
not inherited in the conventional, strictly genetic way, are influenced
by our genetic make-up.
Researchers led by Andrew Feinberg of Johns Hopkins University in
Baltimore looked at changes in the 'methylation' of people's DNA over
time. Attaching methyl groups - which contain one carbon atom - to
particular DNA bases can influence a gene's activity.
Epigenetic changes - potentially reversible changes that do not alter
the actual nucleotide sequence of the DNA but do affect its functioning
- are thought to be involved in many cancers and other diseases of old
age, such as diabetes.
This study is a step towards linking such changes with diseases, says
Feinberg. "The question of whether DNA methylation changes over a
lifetime hadn't been asked before," he says. "A fairly large number of
people thought it didn't change."
All change
To address the question, the researchers analysed samples from 111
Icelandic men and women collected first in the early 1990s, with a
second sample taken, 11 years later on average. By the time of the
second sample, the subjects were aged 69 and over. The results are
reported in the medical journal JAMA 1
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http://www.nature.com/news/2008/080624/full/news.2008.913.html#B1> .
The team measured the level of methylation over the whole genome, using
two enzymes that cut a specific sequence of four DNA letters - CCGG. One
enzyme cuts this sequence only when the second 'C' has a methyl group
attached, the other cuts it regardless. So the difference between the
number of cuts made by each enzyme is a measure of methylation.
Nearly two-thirds of the Icelanders showed at least a 5% change in the
amount of methylation, and in nearly one-third the change was more than
10%. People were equally likely to show more or less methylation: the
range of the change was from -30% to +26%.
Changes in methylation could influence the development of diseases that
are influenced by the complex action of many genes. "This may explain
why some people don't get disease, but we don't know," says team member
Vilmundur Gudnason, of the Icelandic Heart Association in Kopavogur.
Nor do the researchers know why the amount of methylation goes down or
goes up, or how this relates to disease. They plan to address this last
question by comparing the changes in methylation with the individual's
health.
Family clusters
The team repeated the analysis using samples collected from 126
individuals from 21 families living in Utah in the United States. The
average interval between samples was 16 years. As well as looking at
methylation across the genome, they used a different test to analyse
changes in 807 specific genes.
The results were similar: two-fifths of the individuals showed a change
in methylation of at least 5%, with a range of change from -49% to +39%.
In the Utah sample, members of the same family tended to show the same
direction of change. "We were surprised to see such clusters," says
Feinberg.
The four individuals who showed the biggest loss of methylation all
belonged to one family. "It would be worth studying the genetics of this
family on its own," says James Flanagan, who studies epigenetic
influences on cancer at University College London, UK.
