The University Record, November 5, 1997

Researchers present work at American Society for Human Genetics meeting

Scientists from the Medical School presented research results last week at the American Society for Human Genetics meeting in Baltimore.

Ancient 'master control' gene directs limb/genital development from mice to men

One tiny mutation passed on for six generations in the genes of a Michigan family gave Jeff Innis the clue he needed to make a connection between evolutionary and embryological development in mice and humans.

In 1996, Innis and graduate students Douglas Mortlock and Laura Post discovered that a mutation in HOXA13 was responsible for abnormal limb and genital development in mice. Because of another single-point mutation occurring over 100 years ago, he now knows that HOXA13 has the same effect in people.

HOXA13 is one of 39 "master control" genes that regulate embryonic development in vertebrates by coordinating the activity of other genesÑturning them on and off at precise times and locations as the embryo develops. Scientists believe these ancient genes originated millions of years ago when animal life began. Because they play such a vital role in embryological development, they have remained part of the genetic code for all animals.

"Since mutations in HOXA13 appear to produce similar abnormalities in mice and humans, we suspect evolutionary processes affecting development of limbs and the genitourinary tract may have taken place simultaneously in all four-limbed, land-dwelling animals," says Innis, an assistant professor of human genetics. Currently, Innis is studying the role HOXA13 plays in placental biology and why mice who inherit two copies of the mutated gene usually die before birth.

Stripped-down gene may block muscular dystrophy symptoms in mice

Michael A. Hauser, a research fellow in human genetics, has isolated the key components of the gene for dystrophinÑa protein that prevents the progressive muscle deterioration associated with muscular dystrophy. Stripping the enormous 2.5-million-base-pair gene down to its essential elements allows it to fit inside conventional viruses used to transport genes to muscle cells, according to Hauser.

By methodically deleting segments of the gene and then testing its ability to induce dystrophin expression in transgenic mice with the defective gene, Hauser has been able to isolate the 6,000 base-pairs of DNA that are most crucial to dystrophin expression.

"Although this mini-gene is not as effective as the complete version, our experiments indicate it may not have to be," Hauser says. "Expressing just 20 percent of the normal levels of our smaller version of dystrophin is enough to prevent most dystrophic symptoms in muscle tissue from transgenic mice."

Genetic counseling: Patients want PCPs to provide; physicians say don't have time or training

Health care consumers place a high priority on individual choice when it comes to decisions on issues related to genetic testing. Suspicious of bureaucracy and government interference, they say the one person they would turn to for advice is their primary care physician. Physicians, however, say they aren't adequately trained and don't have time to provide genetic counseling for their patients.

This dichotomy between the concerns of consumers and health professionals surfaced during a series of nine Michigan community focus groups designed to collect data on personal values related to genetic testingÑaccording to Diane L. Baker, director of the genetic counseling program at the Medical School.

"Consumers in our focus groups were very ambivalent about genetic testing in general, but believed strongly that it should remain a matter of individual choice," Baker says. "Physicians recognized this ambivalence and saw the need for counseling, but maintained it requires a non-directive approach and more time than they can give during individual patient visits."