The differences, or mutations, in question create minor changes in amino acids -- the building blocks of DNA -- from person to person. Zebrafish can be used as a model to understand what biological effects result from these genetic mutations.
Personalized medicine uses modern technology and tools to find biological and genetic differences in individuals so that treatment is more effectively delivered.
"A major challenge of personalized medicine is the lack of a standard way to define the importance of each of the many unique mutations found in an individual's genetic code," said Keith Cheng, M.D., Ph.D., professor of pathology and lead researcher. "Approaches are particularly needed to experimentally determine what differences these mutations make. It is difficult to distinguish the effects of a single amino acid change caused by those changes in our DNA."
The zebrafish is a good choice 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 Cheng lab's approach is like testing small damages in car parts, one at a time. For example, a "mutant" car headlight is known not to work when a certain connector is missing. Taking a normally functioning connector out of a working headlight and replacing it with a connector damaged in a specific way -- a cracked wire casing or a corroded wire connector, for example -- 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.
Postdoctoral fellow Zurab Tsetskhladze, who performed the zebrafish experiments, tested this method with two genes that affect skin color. He started with an equivalent of the broken car part: mutant zebrafish with lighter pigment cells. First, Tsetskhladze confirmed that by injecting normal messenger RNA (ribonucleic acid) into the mutant zebrafish, the lighter pigment cells become "cured" -- or darker --like those of a normal zebrafish. Messenger RNA makes the cells produce the protein the scientists want to study.
Tsetskhladze was then able to test RNA with only one "human" mutation to see if cure was still 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.
Cheng's lab works with zebrafish to study genetic differences that contribute to human skin color. 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.
In the current study, 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. The researchers found that the change made no difference in function in zebrafish. This finding matched the findings of K.C. Ang, postdoctoral fellow, who found no effect of the tested change on the skin color of East Asians.
To see if this approach might be used in other ways, Stephen Wentzel, graduate student, Penn State College of Medicine, looked at mutations in the four genes known to contribute to albinism, which lightens the color of skin, eyes and hair, and is associated with any one of more than 250 known single amino acid differences. He found that at least 210 of these are theoretically testable in the zebrafish. This new test may help scientists to determine which mutations can be ignored and which may need action – such as a change in life habit.
"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.
Other researchers are Khai C. Ang, Steven M. Wentzel and Katherine P. Reid, all of Jake Gittlen Cancer Research Foundation, Division of Experimental Pathology, Penn State College of Medicine; Victor A. Canfield, Department of Pharmacology, Penn State College of Medicine; Arthur S. Berg, Department of Public Health Sciences, and Stephen L. Johnson, Department of Genetics, Washington University Medical School; and Koichi Kawakami, Division of Molecular and Developmental Biology, National Institute of Genetics, Japan.
This work was funded by a grant from the National Institutes of Health.
Matthew Solovey | EurekAlert!
How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Life Sciences
18.01.2017 | Health and Medicine
17.01.2017 | Earth Sciences