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Feature   | Spring 2008

 

Learning a new language of life

Adding a group of molecules to a gene can change plants' and animals' characteristics much as an author can change literary meaning by adding or subtracting punctuation.

Like a comma makes a reader pause or a period makes a reader stop, certain sets of molecules can attach to a gene and modulate the gene's activity level. These molecules create biochemical changes that act as on/off switches to activate or silence particular genes. A gene's status dictates the orders sent to a cell that control its function and ultimately contributes to disease risk and physical traits in people, animals, plants and other living organisms. It can even affect personality traits.

Researchers, including an interdisciplinary group at Purdue University, increasingly are investigating the how, why and what that flips genetic switches. This science realm is called "epigenetics," from the Greek and Latin meaning "on top of genes."

Even some expected physical and psychological similarities, or phenotypes, between brothers and sisters may not hold true because a gene has been turned on or off abnormally due to epigenetic changes.

 "Epigenetic alteration can lead to differences in appearance or physical condition between so-called identical siblings," says Perry Kirkham, program coordinator in the Purdue Office of the Vice President of Research and one of the driving forces of the university's epigenetic group. "There are no differences in the gene sequence between the siblings, but changes in the regulation of gene expression lead to very obvious differences in the phenotype of the siblings."

Seeking cures for kids

lady at desk and dog

Purdue geneticist Amy Lossie researches "switches" that turn genes on or off during embryo development, research that could lead to treatments for diseases that have devastating effects on children. Canine friend Kai often accompanies Lossie to Purdue, which she says keeps her focused. "I'm much more productive, because having Kai here reminds me to make the most of every minute." The lab mix, fittingly, has a DNA-shaped chew toy. (Photo by Tom Campbell)

For Amy Lossie, epigenetics is a fascinating way to learn more about how genes function and a basis to develop new disease treatments.  "Our ultimate goal is to determine how genes are turned on and off," says Lossie, a Department of Animal Sciences geneticist. "It's intriguing to me that the difference between mice and people is probably not that the two species have different proteins, but that the genes that encode the proteins are turned on or off at different times and/or different places during embryo development."

Eventually, Lossie and other scientists want to be able to control genetic on/off switches that activate or silence genes so they can develop more effective treatment and maybe cures for a host of diseases, including cancer and two that ignited Lossie's investigation into epigenetics—Angelman syndrome and Prader-Willi syndrome.

Prader-Willi youngsters are morbidly obese by age 2 and keep gaining weight, even on very low-calorie diets. Angelman patients lead tough lives, too; most have recurrent seizures and complete lack of verbal skills. Often, these youngsters are wheelchair-bound by about age 5 because of their progressively poor neuromuscular control.

Scientists have found that the same chromosome area is malfunctioning in both Prader-Willi and Angelman children. The difference is that in Prader-Willi syndrome some genes inherited from the father are silenced; in Angelman syndrome it's some of the mother's genes that are turned off.

Currently, Lossie's research is focused on determining how epigenetic events occur and are regulated during embryonic development. Learning this might lead to ways to help people with diseases, such as Prader-Willi or Angelman syndromes.

"What we're trying to do is put the punctuation in so that we can read the DNA and figure out how the genes are turned on and off during mammalian fetal development," she says.

 

 

 

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