Imagine knowing that you're more susceptible to cancer because of nonfunctional genes inherited from your parents.
Such knowledge might soon be available, according to a recent study by Duke researchers, graduate students and undergraduates. Their study, published in the Dec. 3 issue of journal Genome Research, revealed 156 possible "imprinted" genes in the human genome.
Imprinted genes are like mutated genes in that only one copy is functional. The other inherited copy is turned off and silenced by molecular markers from either the mother or father, leaving no back-up if the one working copy is damaged, said Randy Jirtle, professor of radiation oncology at Duke University Medical Center and a senior author of the study.
The importance of these imprinted genes is connected to the epigenome, which is the regulation of genes, he added.
"The copy that's turned off, that's marked in the egg or sperm in the previous generation, that's done by epigenetic mechanisms," Jirtle said. "DNA methylation, chromatin changes, histone marks, that type of thing."
Because the genes are epigenetically marked, they are more susceptible to environmental modifications, said Alexander Hartemink, assistant professor of computer science and a senior author of the study.
Jirtle explained that environmental conditions such as nutrition could turn the gene on or off and can make a person more susceptible to certain diseases and disorders. For example, individuals with two turned-on copies of the gene for insulin-like growth factor II are more prone to have colon, breast or prostate cancer.
"It's a premalignant environment that's present in your body basically," he said.
Since the imprinted genes are already marked in the gamete stages, conditions like cancer, autism and schizophrenia can be detected very early by looking at the epigenome, which can potentially change the whole approach to treatment of such diseases, Jirtle said.
"I think in the long run we're going to understand diseases better, in particular the role that imprinted genes play," he added.
Jirtle said the process to find these imprinted genes required a collaborative effort between biology and computer science, and could not have been done without either one.
"Every imprinted gene that we have is going to have a characteristic DNA pattern for the female-marked ones and the male-marked imprinted genes," Jirtle said. "And if that is the case, we should be able to use computers to find those patterns and they should be uniquely present in genes that are imprinted."
He said two different machine-learning computer programs were used in identifying genes, and the overlap in the results was the 156 possible imprinted genes in the study.
"We used one existing technology and one we had developed in our own lab to do the predictions," said Hartemink, who wrote the algorithm for the program.
Jason Bosko, a senior in the Pratt School of Engineering who helped write the program Sparse Multinomial Logistic Regression, said finding the imprinted genes was similar to a classification problem.
The program had to compare existing information about 40 imprinted and 700 nonimprinted genes to locate unknown imprinted genes in the human genome, he added.
"You tell the computer some genes that are imprinted, and also some genes that are not imprinted, and you provide a set of descriptors, or features, for each of the genes," Hartemink said. "Then the computer considers features and combinations of features that are predictive of genes belonging to one class or the other. Eventually, you train the computer to distinguish between these classes by some complicated function of a subset of the features."
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