Researchers at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins have found a new technology to analyze and understand the secrets of the junk DNA. Junk DNA contains critical regions for controlling gene function.
These genes that regulate various similar actions need not be the same in all species. The study will be published online at Science Express. The researchers used the zebrafish to test mammalian DNA and identify DNA sequences, known as enhancers. These sequences are involved in turning on a gene. They took the particular RET gene which is associated with Hirschsprung disease and multiple endocrine neoplasia (MEN2).
Researchers identified DNA sequences that can control RET by using the technique that they have developed. Hirschsprung disease (congenital megacolon) is a common birth defect marked by bowel obstruction. MEN2 is an inherited predisposition to neuroendocrine cancers. Mutation in enhancers plays a role in human disease progression. But enhancer mutations are difficult to locate as enhancers are located in the 98 % of the human genome that does not code for protein.
This is the best strategy used for studying similar species. But from an evolutionary standpoint, the last common ancestor of human and zebrafish lived more than 300 million years ago. But the Hopkins researchers developed the new system, by which virtually any DNA sequence can be tested for its ability to turn on a marker gene in zebrafish embryos.
The system allows researchers to study more sequences in a shorter period of time. Using this, they identified several human enhancers able to control expression consistent with the zebrafish ret gene. Shannon Fisher, M.D., Ph.D., the study's first author and an assistant professor in cell biology in Johns Hopkins' Institute for Basic Biomedical Sciences said that Zebrafish are small, about a half inch in length, they grow quickly, and are relatively inexpensive to maintain compared to mice or rats.
The researchers plan to extend their research by analyzing the RET enhancers they found to identify other mutations that might contribute to Hirschsprung disease and MEN2. They have also asked the other researchers to collectively build a database of human enhancers. The research was funded by the March of Dimes and the National Institutes of Health.