Posts Tagged ‘genetics’
When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in clinical and research reports.
Now a study by researchers at Brigham and Women’s Hospital (BWH) proposes a new classification system that may standardize how structural chromosomal rearrangements are described. Known as Next-Gen Cytogenetic Nomenclature, it is a major contribution to the classification system to potentially revolutionize how cytogeneticists worldwide translate and communicate chromosomal abnormalities. The study will be published online April 17, 2014 in The American Journal of Human Genetics.
“As scientists we are moving the field of cytogenetics forward in the clinical space,” said Cynthia Morton, PhD, BWH director of Cytogenetics, senior study author. “We will be able to define chromosomal abnormalities and report them in a way that is integral to molecular methods entering clinical practice.”
According to the researchers, advances in next-generation sequencing methods and results from BWH’s Developmental Genome Anatomy Project (DGAP) revealed an assortment of genes disrupted and dysregulated in human development in over 100 cases. Given the wide variety of chromosomal abnormalities, the researchers recognized that more accurate and full descriptions of structural chromosomal rearrangements were needed.
We are a product of our parents. Maybe you have your mother’s large, dark eyes, and you inherited your father’s infectious smile. Both parents contribute one copy, or allele, of each gene to their offspring, so that we have two copies of every gene for a given trait – one from mom, the other from dad. In general, both copies of a gene are switched on or off as an embryo develops into an adult. The “switching on” of a gene begins the process of gene expression that ultimately results in the production of a protein.
Occasionally, a cell will arbitrarily begin to use of one copy of a gene over the other. The activation of only one member of a gene pair is called ”monoallelic gene expression.” In work published today in Developmental Cell, a team of researchers led by Professor David Spector at Cold Spring Harbor Laboratory (CSHL) shows that this random phenomenon is far more likely to be found in mature, developed cell types than in their stem cell precursors. This, in turn, offers an unexpected glimpse of randomness and variability in gene expression.
Cells are exquisitely sensitive to protein amounts: too much or too little can give rise to diseases, including cancer. For example, certain proteins, called tumor suppressors, act as “stop” signals to restrain cell growth. A cell with only half the dosage of such a protein may become the seed of a tumor. Random monoallelic gene expression cuts the amount of a protein by half, suggesting that this type of variability may have significant implications for disease.
Spector and Mélanie Eckersley-Maslin, Ph.D., lead author on the new paper, found that monoallelic gene expression is truly a random process. “It is not deterministic in any way,” says Spector. “This significant amount of flexibility and randomness in gene expression is important for adaptation as a species evolves, but it is unclear how it functions in organisms today.”
To better understand when monoallelic gene expression is established, Spector and his team collaborated with researchers from the European Molecular Biology Laboratory. The team used advanced sequencing technology and analysis tools to globally assess allele usage in two different cell types. They compared embryonic stem cells, which can change, or “differentiate,” into nearly any type of tissue, with cells that had already differentiated into the precursors of neurons. They found a 5.6-fold increase in the number of monoallelically expressed genes in the differentiated cells. “As differentiation occurs, there is a dramatic change in gene expression as a specific program or set of genes is selected to be expressed and a massive reorganization occurs in the nucleus,” says Spector. “It is these enormous changes that lead to stochastic (i.e., variable) monoallelic expression.”
The team was surprised to find that 8% of the monoallelically expressed genes were able to boost their level of expression to compensate for what would otherwise be a shortfall. The researchers speculate that the cell may require higher amounts of protein from those genes. “This work raises many important questions,” says Spector, “such as: how does the cell know how much of each protein to produce? How much flexibility is there? What is the tipping point toward disease?” The team continues to explore these fascinating questions.
This work was supported by the National Institute of General Medical Sciences and the National Cancer Institute, a Genentech Foundation Fellowship, George A. and Marjorie H. Anderson Fellowship, Deutscher Akademischer Austauschdienst Postdoctoral Fellowship, the European Molecular Biology Laboratory, and the Wellcome Trust.
“Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation” appears online in Developmental Cell on February 24, 2014. The authors are: Mélanie A. Eckersley-Maslin, David Thybert, Jan H. Bergmann, John C. Marioni, Paul Flicek, and David L. Spector. The paper can be obtained online at: http://www.cell.com/developmental-cell/home
Thanks to Cold Spring Harbor Laboratory for contributing this story.
A good state of mind — that is, your happiness — affects your genes, scientists say. In the first study of its kind, researchers from UCLA’s Cousins Center for Psychoneuroimmunology and the University of North Carolina examined how positive psychology impacts human gene expression.
“We wanted to determine whether a colony’s genetic diversity has an impact on its survival, and what that impact may be,” says Dr. David Tarpy, an associate professor of entomology at North Carolina State University and lead author of a paper describing the study. “We knew genetic diversity affected survival under controlled conditions, but wanted to see if it held true in the real world. And, if so, how much diversity is needed to significantly improve a colony’s odds of surviving.”
Tarpy took genetic samples from 80 commercial colonies of honey bees (Apis mellifera) in the eastern United States to assess each colony’s genetic diversity, which reflects the number of males a colony’s queen has mated with. The more mates a queen has had, the higher the genetic diversity in the colony. The researchers then tracked the health of the colonies on an almost monthly basis over the course of 10 months – which is a full working “season” for commercial bee colonies.
The researchers found that colonies where the queen had mated at least seven times were 2.86 times more likely to survive the 10-month working season. Specifically, 48 percent of colonies with queens who had mated at least seven times were still alive at the end of the season. Only 17 percent of the less genetically diverse colonies survived. “48 percent survival is still an alarmingly low survival rate, but it’s far better than 17 percent,” Tarpy says.
“This study confirms that genetic diversity is enormously important in honey bee populations,” Tarpy says. “And it also offers some guidance to beekeepers about breeding strategies that will help their colonies survive.”
The paper, “Genetic diversity affects colony survivorship in commercial honey bee colonies,” was published online this month in the journal Naturwissenschaften. Co-authors of the study are Dr. Dennis vanEngelsdorp of the University of Maryland and Dr. Jeffery Pettis of USDA. The work was supported by the USDA Cooperative State Research, Education and
Extension Service, the USDA Agricultural Research Service, the North Carolina Department of Agriculture and Consumer Services and the National Honey Board.
Thanks to NC State University for this story.