New Genomic DNA Modification in Zebrafish Could Help Us Study Human Disease

Did you know that zebrafish, a tropical freshwater fish, are being more commonly used to model and study human diseases? Now, says Phys.org, researchers from the Garvan Institute of Medical Research in Darlinghurst, Sydney, New South Wales have discovered something new about the zebrafish: a novel DNA modification within their genome. Researchers found that a significant amount of ‘TGCT’ DNA repeats in zebrafish undergo methylation. As a result, researchers believe understanding this process could give insight into epigenetics and human disease. You can find the full study data in Nucleic Acids Research. 

Zebrafish

According to a blog post from the Intramural Research Program, up to 70% of human genes are found in zebrafish. Further, the blog explains:

zebrafish have two eyes, a mouth, brain, spinal cord, intestine, pancreas, liver, bile ducts, kidney, esophagus, heart, ear, nose, muscle, blood, bone, cartilage, and teeth. Many of the genes and critical pathways that are required to grow these features are highly conserved between humans and zebrafish.

Thus, zebrafish are an accurate way to model various human diseases. To study the diseases, the blog explains:

Often a patient’s DNA is sequenced in order to find a mutation in a gene that could potentially cause his or her disease symptoms. To determine if loss of function of that gene could cause the symptoms seen in the patient, the same gene is mutated or “knocked-out” in zebrafish, and then the fish are examined for similar symptoms.

Learn more about Zebrafish here.

Recent Research

In the recent research, researchers discovered DNA methylation in TGCT repeats. Within our DNA, we have four lettered bases: C, G, T, and A. In this case, the methylation is happening specifically in TGCT. Usually, methylation occurs in areas where G follows a C; however, there are exceptions, as shown in this case. Alternately, another exception is within Rett syndrome, a rare neurological disorder caused by a gene mutation on the X-chromosome. Learn more about Rett syndrome.

But what is methylation? According to What is Epigenetics?, DNA methylation is:

an epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA, thereby often modifying the function of the genes and affecting gene expression.

Methylation can cause genes to turn on or off, which can either help or hinder certain bodily functions. In this specific research, researchers profiled the zebrafish genome because they wanted to understand methylation outside of “GC” patterns. When ‘TGCT’ repeated, methylation often occurred in that area. Researchers also discovered that while methylation occurred in zebrafish eggs, sperm, and growing embryos, there was no methylation in fertilized zebrafish eggs. Says Dr. Bogdanovic, one of the study’s researchers:

“We believe TGCT methylation to be linked to the awakening of the embryonic genome in zebrafish.”

Later, researchers also determined that the cause of the methylation was Dnmt3ba, a type of enzyme. In the future, researchers hope to learn about how these non-GC methylation processes impact the development of neurological disorders in humans.