Genome study yields clue

The Baltimore Sun

Johns Hopkins researchers who studied the genomes of people in Iceland and Utah say they may have found a clue to why people are increasingly prone to disease as they age.

The answer may not lie specifically in the person's genes, but in chemical changes occurring around the genes that help determine which are active and which are silent.

As a result, a person could become more prone to heart disease, cancer and other diseases of aging because certain genes that used to function no longer do so - or vice versa. Animal studies have shown that such changes can be triggered by environmental forces such as diet.

"It could be that if you ate a lot of food with high levels of metals, or if you smoked, you could have changes over time in the expression of particular genes that cause you to be at risk for disease," said M. Daniele Fallin, an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

Dr. Andrew Feinberg, a professor of molecular biology and genetics at the Hopkins medical school, said the report "opens up a whole new avenue of study." Feinberg was lead author of the study, which appears in today's Journal of the American Medical Association.

Collaborating with scientists at the University of Iceland, the Hopkins researchers studied two populations over time to see if they could observe changes in the amount of "methylation" present in a person's genome.

The term refers to the attachment of methyl groups (molecules of carbon and hydrogen) along the genetic sequence that makes up a person's DNA. They trigger the activation of genes - helping to determine, for instance, why skin cells are different from blood or heart cells despite having identical DNA.

The degree of methylation is part of a person's epigenetics - aspects of an individual's makeup that exist apart from the genes themselves.

The researchers tapped into continuing studies in Utah and Iceland, both havens for genetic research because of homogeneous populations. The researchers obtained DNA samples given over a decade apart by 111 people in Iceland and 126 in Utah.

For each person, they measured the amount of methylation present at each point in time - about a third of the subjects in Iceland and 30 percent in Utah had substantial changes over the period.

In the Utah group, they also discovered that the tendency to undergo epigenetic changes ran in families. In other words, if one person experienced abnormal methylation over time, other members of the family were likely to do so as well.

Feinberg noted that many diseases occurring early in life, such as cystic fibrosis, are caused by the transmission of abnormal genes from parent to child. But others that occur much later in life may be influenced by the interactions of genes and the environment.

Environmental factors can increase the amount and the location of methylation along the genome, influencing whether genes are functioning or not. The changes can also occur randomly, as cells divide and information gets lost or jumbled.

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