Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Finding the Switch: Researchers Create Roadmap for Gene Expression

15.04.2014

In a new study, researchers from North Carolina State University, UNC-Chapel Hill and other institutions have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. Their work also sheds new light on how heredity and environment can affect gene expression.

Pinpointing the genetic causes of common diseases is not easy, as multiple genes may be involved with a disease. Moreover, disease-causing variants in DNA often do not act directly, but by activating nearby genes. To add to the complexity, genetic activation is not like a simple on/off switch on a light, but behaves more like a “dimmer switch” – some people may have a particular gene turned all the way up, while others have it only turned halfway on, completely off, or somewhere in between. And different factors, like DNA or the environment, play a role in the dimmer switch’s setting.

According to Fred Wright, NC State professor of statistics and biological sciences, director of NC State’s Bioinformatics Center and co-first author of the study, “Everyone has the same set of genes. It’s difficult to determine which genes are heritable, or controlled by your DNA, versus those that may be affected by the environment. Teasing out the difference between heredity and environment is key to narrowing the field when you’re looking for a genetic relationship to a particular disease.”

Wright, with co-first author Patrick Sullivan, Distinguished Professor of Genetics and Psychiatry at UNC-Chapel Hill and director of the Center for Psychiatric Genomics, and national and international colleagues, analyzed blood sample data from 2,752 adult twins (both identical and fraternal) from the Netherlands Twin Register and an additional 1,895 participants from the Netherlands Study of Depression and Anxiety. For all 20,000 individual genes, they determined whether those genes were heritable – controlled by the DNA “dimmer switch” – or largely affected by environment.

“Identical twins have identical DNA,” Wright explains, “so if a gene is heritable, its expression will be more similar in identical twins than in fraternal twins. This process allowed us to create a database of heritable genes, which we could then compare with genes that have been implicated in disease risk. We saw that heritable genes are more likely to be associated with disease – something that can help other researchers determine which genes to focus on in future studies.”

The study appears online April 13 in Nature Genetics.

“This is by far the largest twin study of gene expression ever published, enabling us to make a roadmap of genes versus environment,” Sullivan says, adding that the study measured relationships with disease more precisely than had been previously possible, and uncovered important connections to recent human evolution and genetic influence in disease.

The Netherlands Twin Register has followed twin pairs for over 25 years and in collaboration with the longitudinal Netherlands Study of Depression and Anxiety established a resource for genetic and expression studies. Professor Dorret Boomsma, who started the twin register, says, “in addition to the fundamental insights into genetic regulation and disease, the results provide valuable information on causal pathways. The study shows that the twin design remains a key tool for genetic discovery.”

Blood samples from the Netherlands were processed by the NIMH Center for Collaborative Genomics Research on Mental Disorders at Rutgers University. NC State research scholar Yi-Hui Zhou and associate professor of statistics Jung-Ying Tzeng contributed to the work. Funding for the study included grants from the National Institute of Mental Health and other NIH Institutes, the Gillings Innovation Lab, the Netherlands Organization for Scientific Research, the Center for Medical Systems Biology, Biobanking and Biomolecular Resources Research Infrastructure, and the European Science Foundation and European Research Council.

Note to editors: Abstract of the paper follows.

“Heritability and genomics of gene expression in peripheral blood”

DOI:10.1038/ng.2951

Authors: Fred A.Wright, NC State University; Patrick F. Sullivan, UNC-Chapel Hill, et al
Published: Online April 13, 2014 in Nature Genetics

Abstract: We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (~777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of local eQTLs (6,988) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.

Tracey Peake | newswise
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>