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Junk DNA may not be so junky after all

ditionally, DNA sequences are thought to have to look similar to function similarly; this is how scientists identify genes in other species, a strategy best used for studying similar species. From an evolutionary standpoint, the last common ancestor of human and zebrafish lived more than 300 million years ago. Because DNA sequences in each species have changed over time, traditional methods of comparing DNA sequences between humans and zebrafish have failed to identify any potential enhancers around the RET gene because the DNA sequences differ too much.

That drove the Hopkins researchers to seek and develop this 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 is a significant advance over current methods in this model species, allowing 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.

Zebrafish have become the ideal system for doing these types of large scale studies. They are small - only about a half inch in length - they grow quickly, and are relatively inexpensive to maintain compared to mice or rats. "Zebrafish are the only vertebrate embryo you can even think about doing this type of work in," says 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.

The researchers' next steps are further study of the RET enhancers they found to identify other mutations that might contribute to Hirschsprung disease and MEN2, and to entice other investigators to collectively build a database of human enhancers. "If there's one thing we've learned here, it's that we are not very good at recognizing enhancers. We just don't know what they look like," says Fisher. "We are anxious for others to use this technology on their favorite gen
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Source:Johns Hopkins Medical Institutions


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