Our Genome Changes Over Lifetime, And May Explain Many 'Late-onset' Diseases

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Our Genome Changes Over Lifetime, And May Explain Many 'Late-onset'

Diseases

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/06/080624174849.htm

Researchers at s Hopkins have found that epigenetic marks on DNA-

chemical marks other than the DNA sequence-do indeed change over a

person's lifetime, and that the degree of change is similar among

family members. The team suggests that overall genome health is

heritable and that epigenetic changes occurring over one's lifetime

may explain why disease susceptibility increases with age.

" We're beginning to see that epigenetics stands at the center of

modern medicine because epigenetic changes, unlike DNA sequence which

is the same in every cell, can occur as a result of dietary and other

environmental exposure, " says P. Feinberg, M.D., M.P.H, a

professor of molecular biology and genetics and director of the

Epigenetics Center at the s Hopkins School of

Medicine. " Epigenetics might very well play a role in diseases like

diabetes, autism and cancer. "

If epigenetics does contribute to such diseases through interaction

with environment or aging, says Feinberg, a person's epigenetic marks

would change over time. So his team embarked on an international

collaboration to see if that was true. They focused on methylation-

one particular type of epigenetic mark, where chemical methyl groups

are attached to DNA.

" Inappropriate methylation levels can contribute to disease-too much

might turn necessary genes off, too little might turn genes on at the

wrong time or in the wrong cell, " says Vilmundur Gudnason, MD, PhD,

professor of cardiovascular genetics at the University of Iceland

director of the Icelandic Heart Association's Heart Preventive Clinic

and Research Institute. " Methylation levels can vary subtly from one

person to the next, so the best way to get a handle on significant

changes is to study the same individuals over time. "

The researchers used DNA samples collected from people involved in

the AGES Reykjavik Study (formerly the Reykjavik Heart Study). Within

the study, about 600 people provided DNA samples in 1991, and again

between 2002 and 2005. Of these, the research team measured the total

amount of DNA methylation in each of 111 samples and compared total

methylation from DNA collected in 2002 to 2005 to that person's DNA

collected in 1991.

They found that in almost one-third of individuals, methylation

changed over that 11-year span, but not all in the same direction.

Some individuals gained total methylation in their DNA, while others

lost. " What we saw was a detectable change over time, which showed us

proof of the principle that an individual's epigenetics does change

with age, " says M. e Fallin, Ph.D., an associate professor of

epidemiology at the s Hopkins Bloomberg School of Public

Health. " What we still didn't know was why or how, but we

thought 'maybe this, too, is something that's heritable' and could

explain why certain families are more susceptible to certain

diseases. "

The team then measured total methylation changes in a different set

of DNA samples collected from Utah residents of northern and western

European descent. These DNA samples were collected over a 16-year

span from 126 individuals from two- and three-generation families.

Similar to the Icelandic population, the Utah family members also

showed varied methylation changes over time. But they found that

family members tended to have the same kind of change-if one

individual lost methylation over time, they saw similar loss in other

family members.

" We still haven't concretely figured out what this means for health

and disease, but as an epidemiologist, I think this is very

interesting, since epigenetic changes could be an important link

between environment, aging and genetic risk for disease, " Fallin says.

The research was funded by the National Institutes of Health, Swedish

Cancer Foundation, Icelandic Parliament, Huntsman General Clinical

Research Center, W. M. Keck Foundation, S. and Delores Doré

Eccles Foundation, Fulbright Foundation and the Icelandic Student

Innovation Fund.

The research was reported in the June 25 issue of the Journal of the

American Medical Association. Authors on the paper are Hans

Bjornsson, Sigurdsson, Irizarry, Hengmi Cui, Wenqiang

Yu, Rongione, Fallin and Feinberg, all of Hopkins; Thor

Aspelund, Gudny Eiriksdottir and Vilmundur Gudnason of Hjartavernd,

Reykjavik, Iceland; Tomas Ekstrom of Karolinska Institute, Stockholm,

Sweden; Tamara and Lenore Launer of the National Institute on

Aging, Bethesda, Md.; Mark Leppert of University of Utah, Salt Lake

City; and Carmen Sapienza of Temple University Medical School,

Philadelphia, Pa.