Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Individual gene differences can be tested in zebrafish

26.10.2012
The zebrafish is a potential tool for testing one class of unique individual genetic differences found in humans, and may yield information helpful for the emerging field of personalized medicine, according to a team led by Penn State College of Medicine scientists.

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!
Further information:
http://www.psu.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>