Individual gene differences can be tested in zebrafish

The zebrafish is a potential tool for testing one class of unique individual's genetic difference that is found in humans. This research that is conducted by a team of Penn State College of Medicine scientists suggest that this finding may yield information is useful for the emerging field of personalized medicine.

The scientists will use this zebrafish as a model to study what biological effects stem up from genetic mutation.  The personalized medicine uses modern technology and tools to find biological and genetic differences in individuals so that treatment is more effectively delivered. The reason why they chose a zebrafish is because of its similarity to humans as a vertebrate, its transparency as an embryo and the powerful genetic tools available in this model organism.

The approach they made is like testing small damages in car parts. Taking a normally functioning connector out of a working headlight and replacing it with a connector damaged in a specific way can show whether the damage matters. If the light works, then that mutation makes no difference on the function of the headlight. If the light does not work, the mutation has an effect.

With the help of two genes that affect skin color, postdoctoral fellow Zurab Tsetskhladze performed the zebrafish experiments. First, Tsetskhladze confirmed that by injecting normal messenger RNA (ribonucleic acid) into the mutant zebrafish, the lighter pigment cells become darker like those of a normal zebrafish. Messenger RNA makes the cells produce the protein the scientists want to study.

With the help of one human mutation, he was able to test RNS to check if cure was possible. Cure suggests that the mutation does not matter. If cure is prevented by the mutation, the conclusion is that the protein's function is affected by the amino acid difference being tested.

Scientists want to determine the role these differences play in the development of skin cancer, and to find ways to better protect people from cancer.

These findings matched the findings of K.C. Ang, postdoctoral fellow, who found no effect of the tested change on the skin color of East Asians.

The study reveals that the two of the amino acid differences that Cheng has shown in prior studies to contribute to light skin color in humans prevented the zebrafish color from darkening. A third amino acid difference that is common in Eastern Asians was of unknown effect. 

"This approach may potentially be extended to other biological functions and may therefore be useful in personalized medicine," Cheng said.

The researchers published their findings in PLoS ONE.