Posts tagged genomics
Articles and news from the latest research reports.
Stanford/Yale study gives insight into subtle genomic differences among our own cells
Stanford University School of Medicine scientists have demonstrated, in a study conducted jointly with researchers at Yale University, that induced-pluripotent stem cells — the embryonic-stem-cell lookalikes whose discovery a few years ago won this year’s Nobel Prize in medicine — are not as genetically unstable as was thought.
The new study, published online Nov. 18 in Nature, showed that what seemed to be changes in iPS cells’ genetic makeup — presumed to be inflicted either in the course of their generation from adult cells or during their propagation and maintenance in laboratory culture dishes — instead are often accurate reflections of existing but previously undetected genetic variations among the cells comprising our bodies.
That’s good news for researchers hoping to use the cells to study disease or, someday, for regenerative medicine. But it raises the question of whether and to what extent we humans are really walking mosaics whose constituent cells differ genetically from one to the next in possibly significant respects, said Alexander Urban, PhD, assistant professor of psychiatry and behavioral sciences. Urban shared senior authorship of the study with bioinformatics professor Mark Gerstein, PhD, and neurobiology professor Flora Vaccarino, MD, both of Yale.
Is schizophrenia more than one disease?
Schizophrenia wrecks the lives of millions worldwide – and has defeated researchers looking for a single cause. Time for complex new thinking.
PAUL is 21. He thinks the voices started a couple of years ago, but it’s hard to remember exactly because they just seemed to fade in. They whisper insistently, commenting on his actions, trying to control his thoughts and feelings. Living with them is a constant battle, causing him to drop out of college and stop seeing friends. He has been treated in hospital and is being prescribed antipsychotic drugs, but he sees all this as part of a conspiracy.
Paul’s world view is informed by psychosis. This mental state disrupts perception and the interpretation of reality, and is characterised by hallucinations and delusions. Doctors recognise psychosis as a marker for many medical conditions ranging from those caused by electrolyte disturbance to epilepsy, dementia and rare autoimmune disorders.
In Paul’s case these conditions are rapidly excluded. After other short-lived, mood or drug-related causes are also excluded, Paul is diagnosed with schizophrenia - one of a group of disorders characterised by psychosis. But schizophrenia also affects Paul’s emotional and verbal responsiveness, motivation and insight. And it is these functional symptoms that are its most disabling features because they erode the ability to interact with others, maintain social contacts and work.
So what is schizophrenia? In the late 19th century German psychiatrist Emil Kraepelin identified the symptoms and presentation of a disease later called schizophrenia by Eugen Bleuler, a Swiss psychiatrist. Bleuler saw it as an umbrella term for a collection of diseases. Despite attempts to define subtypes or identify specific forms, schizophrenia is still treated broadly as a single disease, and it affects around 1 per cent of adults.
So a shorter, more honest answer to the question of what schizophrenia is would be that we won’t really know until we can define its neurobiological basis. For now, psychosis represents a major frontier in neuroscience because it shakes our certainties about the way we see the world - and understand the brain.
New brain gene born, study shows
Scientists have taken a step forward in helping to solve one of life’s greatest mysteries - what makes us human?
Image: Irish Wildcat
An international team of researchers have discovered a new gene that helps explain how humans evolved from apes. Scientists say the gene - calledmiR-941 - appears to have played a crucial role in human brain development and may shed light on how we learned to use tools and language. Researchers say it is the first time that a new gene - carried only by humans and not by apes - has been shown to have a specific function within the human body.
Unique finding
A team at the University of Edinburgh compared the human genome to 11 other species of mammals, including chimpanzees, gorillas, mouse and rat, to find the differences between them. The results, published in Nature Communications, showed that the gene - miR-941 - is unique to humans. The researchers say that it emerged between six and one million years ago, after humans had evolved from apes. The gene is highly active in two areas of the brain that control our decision making and language abilities. The study suggests it could have a role in the advanced brain functions that make us human.
Startling results
It is known that most differences between species occur as a result of changes to existing genes, or the duplication and deletion of genes. But scientists say this gene emerged fully functional out of non-coding genetic material, previously termed “junk DNA”, in a startlingly brief interval of evolutionary time. Until now, it has been remarkably difficult to see this process in action. Researcher Dr Martin Taylor, who led the study at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, said the results were fascinating.
This new molecule sprang from nowhere at a time when our species was undergoing dramatic changes: living longer, walking upright, learning how to use tools and how to communicate. We’re now hopeful that we will find more new genes that help show what makes us human. -Dr Martin Taylor (Programme leader, Biomedical Systems Analysis)
(Source: ed.ac.uk)
Global Genome Effort Seeks Genetic Roots of Disease
By decoding the genomes of more than 1,000 people whose homelands stretch from Africa and Asia to Europe and the Americas, scientists have compiled the largest and most detailed catalog yet of human genetic variation. The massive resource will help medical researchers find the genetic roots of rare and common diseases in populations worldwide.
The 1000 Genomes Project involved some 200 scientists at Washington University School of Medicine in St. Louis and other institutions. Results detailing the DNA variations of individuals from 14 ethnic groups are published Oct. 31 in the journal Nature. Eventually, the initiative will involve 2,500 individuals from 26 populations.
“With this resource, researchers have a roadmap to search for the genetic origins of diseases in populations around the globe,” says one of the study’s co-principal investigators, Elaine Mardis, PhD, co-director of The Genome Institute at Washington University. “We estimate that each person carries up to several hundred rare DNA variants that could potentially contribute to disease. Now, scientists can investigate how detrimental particular rare variants are in different ethnic groups.”
Scientists deepen genetic understanding of MS
Five scientists, including two from Simon Fraser University, have discovered that 30 per cent of our likelihood of developing Multiple Sclerosis (MS) can be explained by 475,806 genetic variants in our genome. Genome-wide Association Studies (GWAS) commonly screen these variants, looking for genetic links to diseases.
Corey Watson, a recent SFU doctoral graduate in biology, his thesis supervisor SFU biologist Felix Breden and three scientists in the United Kingdom have just had their findings published online in Scientific Reports. It’s a sub-publication of the journal Nature.
An inflammatory disease of the central nervous system, MS is the most common neurological disorder among young adults. Canada has one of the highest MS rates in the world.
Watson and his colleagues recently helped quantify MS genetic susceptibility by taking a closer look at GWAS-identified variants in the major histocompatibility complex (MHC) region in 1,854 MS patients. The region has long been associated with MS susceptibility.
The MS patients’ variants were compared to those of 5,164 controls, people without MS.
They noted that eight percent of our 30-per-cent genetic susceptibility to MS is linked to small DNA variations on chromosome 6, which have also long been associated with MS susceptibility.
The MHC encodes proteins that facilitate communication between certain cells in the immune system. Outside of the MHC, a good majority of genetic susceptibility can’t be nailed down because current studies don’t allow for all variants in our genome to be captured.
“Much of the liability is unaccounted for because current research methods don’t enable us to fully interrogate our genome in the context of risk for MS or other diseases,” says Watson.
The researchers believe that one place to look for additional genetic causes of MS may be in genes that have variants that are rare in the population. “The importance of rare gene variants in MS has been illustrated in two recent studies,” notes Watson, now a postdoctoral researcher at the Mount Sinai School of Medicine in New York.
“But these variants, too, are generally poorly represented by genetic markers captured in GWAS, like the one our study was based on.”
(Source: sfu.ca)
BeerSci: What Beer’s Key Ingredient Reveals About Our Own Genomes
The yeast S. cerevisiae is instrumental in brewing ale. But did you know that it’s also instrumental in helping scientists better understand cells?
Humans have been exploiting S. cerevisiae's fermentation prowess for thousands of years. Without it we wouldn't have beer, bread or wine. In addition to its uses in food production, S. cerevisiae is also an amazing tool for molecular and cell biology, one that is helping scientists suss out the rules of how our cells work and gain clues to what happens at the molecular level when things go wrong.
That’s because S. cerevisiae is one of the simplest eukaryotic cells—cells like those that make up your dog, your houseplants or your local bartender. In fact, in 1996 S. cerevisiae became the first eukaryote to have its genome sequenced. According to the Saccharomyces Genome Database, S. cerevisiae's genome has some 12,100,000 base pairs and some 6,600 open reading frames (that is, places in the genome that could possibly contain a gene).
Most of you, I am sure, remember that there are two general kinds of cells: prokaryotic and eukaryotic. That is, “no nucleus” and “has a nucleus.” That’s all true, but the differences between the two kinds of cells are much more profound than that. Bacteria — prokaryotes — organize their genetic material in a completely different (and much simpler) way than do eukaryotes. Prokaryotes usually only have a chunk of DNA for a genome — usually circular — and a few extra chunks, called plasmids, kicking around in the cytosol. Those plasmids are really useful in doing things like sharing genes between bacteria, and its how one antibiotic-resistant strain of bacteria can pass along antibiotic resistance to a bunch of nigh-unrelated strains of bacteria in, say, your intestines. The genes in bacteria are generally read exactly as they are found in the DNA, kind of like how you’re reading this sentence. No intervening clumps of letters to clutter things up.
Eukaryotes, on the other hand, bundle up all that DNA (and they have a lot of it) into a protein-DNA complex called chromatin, then wind that chromatin into individual chromosomes. Further, the genes are constructed in such a way that they must be heavily processed before they can ever “code” for a functional protein. Much of what we understand about eukaryotic cellular processes and eukaryotic gene expression, we learned by studying the molecular mechanics of S. cerevisiae.
About face: Study shows long-ignored segments of DNA play role in coordinating early stages of face development
The human face is a fantastically intricate thing. The billions of people on the planet have faces that are individually recognizable because each has subtle differences in its folds and curves. How is the face put together during development so that, out of billions of people, no two faces are exactly the same?
School of Medicine researcher Joanna Wysocka, PhD, and her colleagues have discovered key genetic elements that guide the earliest stages of the process.
Their research, published in the Sept. 13 issue of Cell Stem Cell, provides a resource for others studying facial development and could give insights to the cause of some facial birth defects. Because there is not enough genetic information in the body to define exactly where each cell will go, development of the face proceeds much like origami: genes provide instructions for folding, crimping, and movement of cells. As with origami, following a sequence of simple instructions can result in a complex, intricate object.
Wysocka focused on the first critical fold in the process of making an embryo, when the whole of the embryo is a flat sheet of cells that creases and closes over on itself to make a tube. Much of the tube eventually becomes the foundation of the brain and the spinal column, but one end sets the stage for the formation of the head and face. This process is driven by a small population of remarkable cells called neural crest cells.
"We were interested in identifying the portions of the human genome that are responsible for the behavior of the neural crest," Wysocka said.
What they discovered is that the modification of a collection of DNA sequences called “enhancers” can dial up or down the activity of the genes governing which cells eventually become the face. It’s almost as if they have discovered how the instructions for a piece of origami can be modified — slightly change how a fold is made and you may end up with something very different looking.
McGill researchers link genetic mutation to psychiatric disease and obesity
McGill researchers link genetic mutation to psychiatric disease and obesity
Deletion of brain-derived neurotrophic factor leads to major depression, anxiety, and obesity
McGill researchers have identified a small region in the genome that conclusively plays a role in the development of psychiatric disease and obesity. The key lies in the genomic deletion of brain-derived neurotrophic factor, or BDNF, a nervous system growth factor that plays a critical role in brain development.
To determine the role of BDNF in humans, Prof. Carl Ernst, from McGill’s Department of Psychiatry, Faculty of Medicine, screened over 35,000 people referred for genetic screening at clinics and over 30,000 control subjects in Canada, the U.S., and Europe. Overall, five individuals were identified with BDNF deletions, all of whom were obese, had a mild-moderate intellectual impairment, and had a mood disorder. Children had anxiety disorders, aggressive disorders, or attention deficit-hyperactivity disorder (ADHD), while post-pubescent subjects had anxiety and major depressive disorders. Subjects gradually gained weight as they aged, suggesting that obesity is a long-term process when BDNF is deleted.
"Scientists have been trying to find a region of the genome which plays a role in human psychopathology, searching for answers anywhere in our DNA that may give us a clue to the genetic causes of these types of disorders," says Prof. Ernst, who is also a researcher at the Douglas Mental Health University Institute. "Our study conclusively links a single region of the genome to mood and anxiety."
The findings, published in the Archives of General Psychiatry, reveal for the first time the link between BDNF deletion, cognition, and weight gain in humans. BDNF has been suspected to have many functions in the brain based on animal studies, but no study had shown what happens when BDNF is missing from the human genome. This research provides a step toward better understanding human behaviour and mood by clearly identifying genes that may be involved in mental disorders.
"Mood and anxiety can be seen like a house of cards. In this case, the walls of the house represent the myriad of biological interactions that maintain the structure," says Ernst, "Studying these moving parts can be tricky, so teasing apart even a single event is important. Linking a deletion in BDNF conclusively to mood and anxiety really tells us that it is possible to dissect the biological pathways involved in determining how we feel and act.
We now have a molecular pathway we are confident is involved in psychopathology,” adds Ernst, “Because thousands of genes are involved in mood, anxiety, or obesity, it allows us to root our studies on a solid foundation. All of the participants in our study had mild-moderate intellectual disability, but most people with these cognitive problems do not have psychiatric problems – so what is it about deletion of BDNF that affects mood? My hope now is to test the hypothesis that boosting BDNF in people with anxiety or depression might improve brain health.”
(Source: fiercebiotechresearch.com)
The Date of Interbreeding between Neandertals and Modern Humans
Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000–65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.
Genetic diseases diagnosed within 50 hours
The new technology screens the whole genome of the baby from a drop of their blood before homing in on abnormalities in single genes that could explain their ill health.
Genetic diseases are thought to affect up to one in a hundred children and are one of the leading causes of admission to intensive care units immediately after birth.
In about 500 of the conditions - including Krabbe disease, a nervous system disorder - early treatment can prevent the development of severe disability and life-threatening symptoms.
Most of the diseases are extremely rare and many are unfamiliar to doctors, but analysing a baby’s genes to find the cause of their condition currently takes up to six weeks.
Researchers from Children’s Mercy Hospital in Kansas City said this could be cut down to 50 hours using the new method, described in the Science Translational Medicine journal.