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Scientists Build Map of Imprinted Genes

By Tracy Hampton, PhD, JAMA

31 December 2007: While imprinted genes have been linked to a variety of diseases, until now only several dozen have been identified. But a new report reveals a map of 156 new likely imprinted genes scattered throughout the human genome (Luedi PP et al. Genome Res. 2007;17[12]:1723-1730).

Unlike the majority of genes—in which both the maternally and paternally inherited copies are active—in imprinted genes, one of these copies is silenced.

"We're hoping this new roadmap will help us and others find more information about how these genes affect our health and well-being," said Randy Jirtle, PhD, a genetics researcher in the departments of radiation oncology and pathology at Duke University in Durham, NC, and a senior author of the study.

Jirtle and colleagues used DNA sequence information from known imprinted genes to uncover other genes likely to be imprinted. Two of the identified genes were studied in depth and validated as imprinted genes. The KCNK9 (potassium channel, subfamily K, member 9) gene is expressed predominantly in the brain and is a known cancer-causing oncogene. It also may play a role in bipolar disorder and epilepsy because it encodes a potassium ion channel that mediates neuronal excitability. The other validated gene, DLGAP2 (disks large-associated protein 2), is a candidate bladder cancer tumor suppressor. Both of these genes lie on chromosome 8, which had not previously been suspected to contain imprinted genes.

Many of the other newly identified imprinted genes lie within chromosomal regions that have been linked to the development of such diseases as cancer, diabetes, and autism. But more work is needed to determine if the genes play an active role in these disorders and whether they might be used in strategies for disease prevention and management.

Scientists suggest that manipulating imprinted genes to improve health may be feasible because imprinting is an epigenetic phenomenon that can change a gene's function without altering the sequence of its DNA, and it can be influenced by external factors. "Imprinted genes are unusually vulnerable to pressures in our environment," said Jirtle.

More research is needed to determine whether all of the new genes found in this study are truly imprinted—and if other imprinted genes remain to be identified.