(Press-News.org) Contact information: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Capturing a hard-wired variability
Single cell analysis captures a genomic phenomenon that fuels the complexity and diversity of living things
January 09, 2013, New York, NY– A Ludwig Cancer Research study has uncovered a phenomenon that alters prevailing views of how the genome is expressed to make and sustain the life of mammals. Published in the journal Science, the paper helps explain why genetically identical animals are sometimes so different in their biology and appearance, and why some inherited disorders caused by a shared set of aberrant genes can be of such variable severity in different people.
"We have captured a fundamental randomness at the level of gene expression that has never before been described—one that persists throughout development and into adulthood," says Ludwig scientist Rickard Sandberg at the Karolinska Institutet in Sweden. The discovery was made possible by a powerful new technique developed by Sandberg's lab for analyzing the global expression of genes in single cells.
With the exception of a subset of genes found on sex chromosomes, every mammal inherits one copy of every gene from each of its parents. Each of those copies is known as an allele, and alleles often differ measurably from their genomic siblings—a fact that accounts for a good deal of human and animal diversity. It has, however, long been unclear whether each allele in any given cell or organism is expressed equally, or whether one allele is favored over the other. The current study finds that only one allele is expressed in between 12 and 24 percent of all such pairs encoded by the mouse genome. Further, the selection of expressed alleles varies randomly from cell to cell, and switches frequently between the two options throughout their lives.
Biologists typically assume that most alleles, with a few exceptions, are equally expressed on all chromosomes except those that determine sex. They have long known, however, that "imprinted" genes—which may be modified to selectively express only one of the two alleles—are an exception. But such genes only account for 1 percent of the total. "We find that for those genes that are not imprinted, roughly one in five alleles is randomly and dynamically expressed only one at a time," says Sandberg. "And if one allele is being expressed, the other doesn't know about it. There's no coordination between two."
This explains in some measure why identical twins—products of nearly identical genomes—can be noticeably different from one another in their appearance and propensity for disease. Living things are, after all, built from cells, and each cell is in turn the product of the genes it expresses. Dynamic and random allelic expression can result in different blends of some traits, even in otherwise genetically identical people.
The finding also has significant implications for our understanding of some genetic diseases, such as neurofibromatosis, a painful disorder characterized by the systemic proliferation of non-cancerous neural tumors. It has long been a mystery why people who share the mutations that cause this family of diseases are so variably affected by it. The essential randomness of allelic expression might help account for those differences in this disease as well as in others.
###
Funding support for this research was provided by the Ludwig Institute for Cancer Research, the Swedish Research Council grants 2011-965 (Q.D.) and 2008-4562 (R.S.), by the European Research Council Starting Grant 243066 (R.S.), by the Foundation for Strategic Research (R.S.) and Åke Wiberg Foundation grant 756194131 (R.S.). Sequence data have been deposited in NCBI Gene Expression Omnibus (GSE45719) and Sequence Read Archive (SRP020490).
About Ludwig Cancer Research
Ludwig Cancer Research is an international collaborative network of acclaimed scientists with a 40-year legacy of pioneering cancer discoveries. Ludwig combines basic research with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Founded by American shipping magnate, Daniel K. Ludwig, Ludwig Cancer Research has invested $2.5 billion in research to date. Today, the scientific efforts endowed through his resources encompass the Ludwig Institute for Cancer Research and the Ludwig Centers at six U.S. institutions, all pursuing breakthroughs that will alter the course of cancer. For more information about Ludwig Cancer Research, visit http://www.ludwigcanceresearch.org
Rickard Sandberg is an assistant member at the Ludwig Institute for Cancer Research and associate professor and principal investigator at the Department of Cell and Molecular Biology, Karolinska Institutet.
More information, including a copy of the paper, can be found online at the Science press package at http://www.eurekalert.org/jrnls/sci. You will need your user ID and password to access this information
For further information please contact Rachel Steinhardt, rsteinhardt@licr.org or +1-212-450-1582.
Capturing a hard-wired variability
Single cell analysis captures a genomic phenomenon that fuels the complexity and diversity of living things
2014-01-10
ELSE PRESS RELEASES FROM THIS DATE:
Study dispels theories of Y chromosome's demise
2014-01-10
Study dispels theories of Y chromosome's demise
Stripped-down chromosome retains key genes for fertility
A comparison of Y chromosomes in eight African and eight European men dispels the common notion that the Y's genes are mostly unimportant and ...
Penn research helps lay out theory for metamaterials that act as an analog computer
2014-01-10
Penn research helps lay out theory for metamaterials that act as an analog computer
The field of metamaterials has produced structures with unprecedented abilities, including flat lenses, invisibility cloaks and even optical "metatronic" devices that can manipulate ...
Moderate coffee consumption does not lead to dehydration
2014-01-10
Moderate coffee consumption does not lead to dehydration
Researchers dispel the myth that coffee consumption can cause dehydration
New research(1), published today in the PLOS ONE, has found no evidence for a link between moderate coffee consumption and dehydration. The ...
Ahoy! First ocean vesicles spotted
2014-01-10
Ahoy! First ocean vesicles spotted
Scientists discover extracellular vesicles produced by ocean microbes
CAMBRIDGE, Mass-- Marine cyanobacteria — tiny ocean plants that produce oxygen and make organic carbon using sunlight and CO2 — are primary engines of ...
UNC research demonstrates 'guided missile' strategy to kill hidden HIV
2014-01-10
UNC research demonstrates 'guided missile' strategy to kill hidden HIV
The finding provides a new route to killing persistent HIV-infected cells -- a major roadblock to a cure
CHAPEL HILL, NC – Researchers at the UNC School of Medicine have ...
Marine tubeworms need nudge to transition from larvae state
2014-01-10
Marine tubeworms need nudge to transition from larvae state
Intriguing bacterium-animal interaction may have implications for boat owners and the mariculture industry, UH Manoa researchers say
A common problem at Pearl Harbor, biofouling affects harbors ...
Target canine 'superspreaders' to halt killer disease and cull fewer dogs, study suggests
2014-01-10
Target canine 'superspreaders' to halt killer disease and cull fewer dogs, study suggests
A new way to test for the parasite which causes the fatal disease leishmaniasis could help control its spread to humans and stop dogs being needlessly killed in parts ...
New clues to how bacteria evade antibiotics
2014-01-10
New clues to how bacteria evade antibiotics
Scientists have made an important advance in understanding how a subset of bacterial cells escape being killed by many antibiotics.
Cells become "persisters" by entering a state in which they stop replicating and ...
Prediction of the future flu virus
2014-01-10
Prediction of the future flu virus
Every year, influenza outbreaks claim hundreds of thousands of human lives. Though vaccination against flu is fairly efficient, the disease is difficult to exterminate because of the high evolutionary rate of the flu virus. ...
Researchers develop test to predict early onset of heart attacks
2014-01-10
Researchers develop test to predict early onset of heart attacks
LA JOLLA, CA – A new "fluid biopsy" technique that could identify patients at high risk of a heart attack by identifying specific cells as markers in the bloodstream has been developed by a group of ...
LAST 30 PRESS RELEASES:
Cercus electric stimulation enables cockroach with trajectory control and spatial cognition training
Day-long conference addresses difficult to diagnose lung disease
First-ever cardiogenic shock academy features simulation lab
Thirty-year mystery of dissonance in the “ringing” of black holes explained
Less intensive works best for agricultural soil
Arctic rivers project receives “national champion” designation from frontiers foundation
Computational biology paves the way for new ALS tests
Study offers new hope for babies born with opioid withdrawal syndrome
UT, Volkswagen Group of America celebrate research partnership
New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll
Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes
University of Cincinnati Cancer Center presents research at AACR 2025
Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025
AACR: Researchers share promising results from MD Anderson clinical trials
New research explains why our waistlines expand in middle age
Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker
Chips off the old block
Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia
Cutting the complexity from digital carpentry
Lung immune cell type “quietly” controls inflammation in COVID-19
Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity
State and sociodemographic trends in US cigarette smoking with future projections
Young adults drive historic decline in smoking
NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research
Chimpanzee stem cells offer new insights into early embryonic development
This injected protein-like polymer helps tissues heal after a heart attack
FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology
In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity
Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects
A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions
[Press-News.org] Capturing a hard-wired variabilitySingle cell analysis captures a genomic phenomenon that fuels the complexity and diversity of living things