Frogs Help Scientists Understand Childhood Heart Disease

We recently came across a fascinating article in Nature News, “Frogs and Humans Are Kissing Cousins.” You might be surprised to learn that you have a whole lot more in common with frogs than you thought—at a genetic level, anyway. The gene order of the Western Clawed Frog (Xenopus tropicalis) shows surprising similarity to that of mammals. This frog joins a list of sequenced model organisms, including the mouse, zebrafish, nematode, and fruit fly. This amphibian’s genome closely resembles that of the mouse and the human, with large sections of frog DNA on several chromosomes having genes arranged in the same order as in that in mammals. Yet this close genomic relationship doesn’t hold true for some other vertebrates.

Because of this similarity in genome sequence, the frog can be used as a human disease model. Within conserved sequences in the Western Clawed Frog, the researchers found genes that are similar to 80% of human genes known to be associated with diseases. As quoted in the article, Frank Conlon, a geneticist at the University of North Carolina in Chapel Hill, said,”It’s going to make genetic screens in Xenopus immediately more useful.”

courtesy of AnMed Health (www.anmedhealth.org)

As reported recently in an article, “Frogs Help Scientists Combat Childhood Heart Disease,” in the Yale Daily News, for example, a study by Yale cardiology researchers has found a number of genes that can be used to diagnose and treat children who have a birth defect called heterotaxy, which causes the heart to be severely malformed. Their findings, published in late January, suggest that certain genes that affect human embryonic development can cause abnormalities leading to congenital heart disease.

One percent of all newborns develop congenital heart disease, and most patients need surgery to survive. But even with a procedure, outcomes can often be poor and patients may require constant medical supervision over the years.

In children who have heterotaxy, the body cannot properly place the organs on the left or right sides, which causes problems because normal human hearts sit on the left side of our bodies. The left and right side of the heart also perform very different functions: the right side pumps blood to lungs, while the left pumps blood to the body,  so correct placement of the heart in the body is extremely important.

But this study will help scientists better understand what causes congenital heart disease and will give researchers some idea of which genes lead to better or worse outcomes. As quoted in the article, Mustafa Khohka, assistant professor of pediatrics and genetics at Yale, and a co-author of the paper, said, “We also hope to improve our understanding of the genes that affect left-right [axis] development and the mechanisms involved in determining your left side from your right side.”

Frogs make a good model for studying heterotaxy in human embryos, he explained, because the left-right axis develops the same way in both humans and frogs. By examining the number of genetic copy variations in frogs, the scientists were able to identify genes that cause left-right axis mutations. Unfortunately, the findings may not benefit children with heterotaxy for some time.

“Patients with heterotaxy defects include some of the most severely affected individuals we see,” said Dr. Anne M. Murphy, professor of pediatric cardiology at Johns Hopkins University, as quoted in the article. “While discovery of the root causes of the disorder will not immediately translate into better care, there are already emerging examples in our field where understanding the molecular pathways of disease affecting the heart could offer new therapies.”

The researchers were recently awarded a grant by the National Institutes of Health which will fund their studies for the next five years. The group plans to identify more patients with congenital heart disease and the mutations that may have caused it.

We think this study is just one more reason to kiss a frog today!