Our genome changes over lifetime, Johns Hopkins experts say

May explain many 'late-onset' diseases
Researchers at Johns 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. Reporting in the June 25 issue of the Journal of the American Medical Association, 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 Andrew P. Feinberg, M.D., M.P.H, a professor of molecular biology and genetics and director of the Epigenetics Center at the Johns 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. Daniele Fallin, Ph.D., an associate professor of epidemiology at the Johns 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.

Source: Johns Hopkins Medical Institutions

Related stories:

Methylation levels key to glioblastoma survival
A new study analyzing gene expression among patients with glioblastomas has found that not all of the common, deadly brain tumors appear the same upon closer examination.
Scientists develop new, more sensitive nanotechnology test for chemical DNA modifications
Researchers at The Johns Hopkins University School of Medicine in Baltimore have developed a novel test to screen for chemical modifications to DNA known as methylation. The technology potentially could be used both for early cancer diagnoses and for assessing patients' response to cancer therapies.
Rodent studies suggest mother's diet can affect genes and offspring's risk of allergic asthma
A pregnant mouse's diet can induce epigenetic changes that increase the risk her offspring will develop allergic asthma, according to researchers at National Jewish Health and Duke University Medical Center. Pregnant mice that consumed diets high in supplements containing methyl-donors, such as folic acid, had offspring with more severe allergic airway disease than offspring from mice that consumed diets low in methyl-containing foods. The results of the study are being published Sept. 18, 2008, in the online version of the Journal of Clinical Investigation and will appear in the October print issue.
Structure of key epigenetics component identified
Scientists from the Structural Genomics Consortium (SGC) have determined the 3D structure of a key protein component involved in enabling "epigenetic code" to be copied accurately from cell to cell.
DNA editing tool flips its target
Imagine having to copy an entire book by hand without missing a comma. Our cells face a similar task every time they divide. They must duplicate both their DNA and a subtle pattern of punctuation-like modifications on the DNA known as methylation.
Study identifies changes to DNA in major depression and suicide
Autopsies usually point to a cause of death but now a study of brain tissue collected during these procedures, may explain an underlying cause of major depression and suicide. The international research group, led by Dr. Michael O. Poulter of Robarts Research Institute at The University of Western Ontario and Dr. Hymie Anisman of the Neuroscience Research Institute at Carleton University, is the first to show that proteins that modify DNA directly are more highly expressed in the brains of people who commit suicide.
'Smothered' genes combine with mutations to yield poor outcome in cancer patients
Johns Hopkins Kimmel Cancer Center researchers have identified a set of genes in breast and colon cancers with a deadly combination of traditional mutations and "smothered" gene activity that may result in poor outcomes for patients.
The epigenetics of increasing weight through the generations
Overweight mothers give birth to offspring who become even heavier, resulting in amplification of obesity across generations, said Baylor College of Medicine researchers in Houston who found that chemical changes in the ways genes are expressed – a phenomenon called epigenetics -- could affect successive generations of mice.

News discussion:

Medicine & Health news