Imprinted gene found on human chromosome 19

December 30, 2000

DURHAM, N.C. -- Duke University Medical Center researchers report that an unusual gene-control mechanism called "imprinting" is at work on human chromosome 19. For imprinted genes, the gene copy that is turned on depends only on whether it came from the mother or father, rather than on the classic laws of Mendelian genetics, where genes are either dominant or recessive.

In the Jan. 1, 2001, issue of Genomics, the researchers report that a particular gene called PEG3, or paternally expressed gene 3, is imprinted in humans, just as it is in mice. Mouse studies have shown that only the copy of PEG3 that is inherited from the father is functional, and the Duke researchers now have confirmed that is true in humans as well.

"Just because you have an imprinted gene in the mouse doesn't mean it's going to be imprinted in humans," said principal investigator Randy Jirtle, professor of radiation oncology and member at the Duke Comprehensive Cancer Center. "This is also the first evidence of imprinting on human chromosome 19."

Imprinted genes usually occur in clusters, so the researchers are now looking for other imprinted genes in the region of chromosome 19 near PEG3, said Duke's Susan Murphy, lead author of the study, which was funded by the National Institutes of Health. To date, about 40 imprinted genes have been identified in humans, primarily on regions of chromosomes 7, 11 and 15.

Generally speaking, imprinting is not reversible if the functional copy becomes faulty, the non-working copy can't be turned on. The region of chromosome 19 that contains PEG3 has already been linked to ovarian cancer and gliomas, a form of brain cancer.

"Imprinted genes are particularly susceptible to complete loss of function or inappropriate overexpression, and have been implicated in a number of diseases as well as neurobehavioral disorders, including autism," said Murphy, a research associate in radiation oncology whose older son's death from cancer and younger son's diagnosis of autism prompted her to enter imprinting research.

Earlier this year, other Duke researchers reported preliminary findings that suggest imprinted regions on chromosomes 7 and 15 are involved in autism.

In addition to being the first evidence of imprinting on chromosome 19, the PEG3 findings indicate the possibility that the similarities between the human and mouse versions of the gene might extend to behavior changes caused by loss of the gene's function in mice, the researchers said.

Cambridge researchers reported last year that female mice that inherited a faulty PEG3 gene from their fathers leaving them without a functional copy of this gene demonstrated severe nurturing deficiencies that resulted in the deaths of most of their offspring.

"We don't know if there are behavioral changes associated with loss of this gene in humans," emphasized Jirtle. "What we do know is that, in humans, PEG3 is imprinted in the tissues we tested and that it remains imprinted throughout development and adulthood."

The PEG3 gene codes for a protein believed to be involved in transcription, one of the steps in reading genetic material to make proteins. Scientists speculate the nurturing problems seen in mice without PEG3 might be caused by "downstream" effects genes whose expression would normally be aided by the PEG3 protein rather than by a lack of PEG3 itself.

While no behavioral impact has been established for the human PEG3 gene, Jirtle noted that advancing technologies make it easier to identify genes and clarify their functions.

"For a long period of time, it was believed that nurturing controlled behavior," he said. "In mice, it's been shown that genes can have a profound impact on behavior, even on what might be thought of as the most fundamental behavior of mother and offspring."
Co-author of the study is Andrew Wylie, a research associate funded by AstraZeneca Pharmaceuticals Ltd., Cheshire, UK.

Duke University Medical Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to