Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study finds a patchwork of genetic variation in the brain

04.11.2013
Salk scientists find a surprising degree of variation among genomes of individual neurons from the same brain

It was once thought that each cell in a person's body possesses the same DNA code and that the particular way the genome is read imparts cell function and defines the individual.

For many cell types in our bodies, however, that is an oversimplification. Studies of neuronal genomes published in the past decade have turned up extra or missing chromosomes, or pieces of DNA that can copy and paste themselves throughout the genomes.

The only way to know for sure that neurons from the same person harbor unique DNA is by profiling the genomes of single cells instead of bulk cell populations, the latter of which produce an average. Now, using single-cell sequencing, Salk Institute researchers and their collaborators have shown that the genomic structures of individual neurons differ from each other even more than expected. The findings were published November 1 in Science.

"Contrary to what we once thought, the genetic makeup of neurons in the brain aren't identical, but are made up of a patchwork of DNA," says corresponding author Fred Gage, Salk's Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease.

In the study, led by Mike McConnell, a former junior fellow in the Crick-Jacobs Center for Theoretical and Computational Biology at the Salk, researchers isolated about 100 neurons from three people posthumously. The scientists took a high-level view of the entire genome---- looking for large deletions and duplications of DNA called copy number variations or CNVs---- and found that as many as 41 percent of neurons had at least one unique, massive CNV that arose spontaneously, meaning it wasn't passed down from a parent. The CNVs are spread throughout the genome, the team found.

The miniscule amount of DNA in a single cell has to be chemically amplified many times before it can be sequenced. This process is technically challenging, so the team spent a year ruling out potential sources of error in the process.

"A good bit of our study was doing control experiments to show that this is not an artifact," says Gage. "We had to do that because this was such a surprise---- finding out that individual neurons in your brain have different DNA content."

The group found a similar amount of variability in CNVs within individual neurons derived from the skin cells of three healthy people. Scientists routinely use such induced pluripotent stem cells (iPSCs) to study living neurons in a culture dish. Because iPSCs are derived from single skin cells, one might expect their genomes to be the same.

"The surprising thing is that they're not," says Gage. "There are quite a few unique deletions and amplifications in the genomes of neurons derived from one iPSC line."

Interestingly, the skin cells themselves are genetically different, though not nearly as much as the neurons. This finding, along with the fact that the neurons had unique CNVs, suggests that the genetic changes occur later in development and are not inherited from parents or passed to offspring.

It makes sense that neurons have more diverse genomes than skin cells do, says McConnell, who is now an assistant professor of biochemistry and molecular genetics at the University of Virginia School of Medicine in Charlottesville. "The thing about neurons is that, unlike skin cells, they don't turn over, and they interact with each other," he says. "They form these big complex circuits, where one cell that has CNVs that make it different can potentially have network-wide influence in a brain."

Spontaneously occurring CNVs have also been linked to risk for brain disorders such as schizophrenia and autism, but those studies usually pool many blood cells. As a result, the CNVs uncovered in those studies affect many if not all cells, which suggests that they arise early in development.

The purpose of CNVs in the healthy brain is still unclear, but researchers have some ideas. The modifications might help people adapt to new surroundings encountered over a lifetime, or they might help us survive a massive viral infection. The scientists are working out ways to alter genomic variability in iPSC-derived neurons and challenge them in specific ways in the culture dish.

Cells with different genomes probably produce unique RNA and then proteins. However, for now, only one sequencing technology can be applied to a single cell.

"If and when more than one method can be applied to a cell, we will be able to see whether cells with different genomes have different transcriptomes (the collection of all the RNA in a cell) in predictable ways," says McConnell.

In addition, it will be necessary to sequence many more cells, and in particular, more cell types, notes corresponding author Ira Hall, an associate professor of biochemistry and molecular genetics at the University of Virginia. "There's a lot more work to do to really understand to what level we think the things we've found are neuron-specific or associated with different parameters like age or genotype," he says.

Other authors on the study are Michael Lindberg and Svetlana Shumilina of the Department of Biochemistry and Molecular Genetics at the University of Virginia School of Medicine; Kristen Brennand, now at the Icahn School of Medicine at Mount Sinai in New York; Julia Piper, now at Harvard University in Cambridge, Massachusetts; Thierry Voet and Joris Vermeesch of the Center for Human Genetics, KU Leuven, Leuven, Belgium; Chris Cowing-Zitron of Salk's Laboratory of Genetics; and Roger Lasken of the J. Craig Venter Institute in San Diego.

This work was supported by the Crick-Jacobs Center for Theoretical and Computational Biology, the G. Harold & Leila Y. Mathers Foundation, the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, the JPB Foundation, and the Burroughs Wellcome Fund.

About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark

Kat Kearney | EurekAlert!
Further information:
http://www.salk.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>