In 1933, Thomas H. Morgan was awarded the Nobel Prize in Physiology or Medicine for his discoveries concerning the role played by the chromosome in heredity. Much of his research involved breading Drosophila melanogaster, in which he demonstrated sex linkage of the gene for white eyes in the fly. While Morgan ultimately received a Nobel Prize for his work, the real stars of his experiments, the fruit flies, had to be satisfied with much less recognition. In response, several of his subjects composed a song expressing their dissatisfaction with the way they have been treated. Here is their song:
Posts Tagged ‘genetics’
Another day, another study on the health benefits or detriments of habitual coffee drinking. Good for you. Bad for you. Good for your heart, bad for your kidneys. Good for your kidneys, bad for your heart…You get the drift. It seems like there are two distinct camps that have lined up behind each opinion. In the “coffee is healthy” camp you have the coffee lovers and in the other camp are the non-coffee drinkers. As a coffee consumer, I have ignored much of the negative research and have helped spread the positive findings about the benefits of high caffeine consumption to all of my family and friends. However, according to a new large-scale study led by Harvard School of Public Health and Brigham and Women’s Hospital researchers, the debate can now be settled by genetics.
Read the full story on the Harvard University website.
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.