Posts tagged genetics
Articles and news from the latest research reports.
![Scientists have found that one gene is responsible for variability in locomotion in horses and mice.
Traits such as height are controlled by the interaction of up to 700 genes. So it came as quite a shock to researchers from Uppsala University (UU) and their international collaborators that the mutation of just a single gene is responsible for variability in locomotion in horses and mice. Furthermore, the research team discovered that this gene, DMRT3, is expressed in a previously unknown set of neurons in the spinal cord. These findings provide insight into the neural circuits that coordinate movement in vertebrates.
“The amazing result was that we found one very strong signal on one chromosome which by further work led to the discovery of the DMRT3 mutation,” explains Leif Andersson, co-author of the paper published in Nature, from UU and Swedish University of Agricultural Sciences. “This was unexpected since we had [anticipated] a much more complex genetic background for a trait like this.”](http://33.media.tumblr.com/tumblr_ma13qp01ib1rog5d1o1_500.gif)
Scientists have found that one gene is responsible for variability in locomotion in horses and mice.
Traits such as height are controlled by the interaction of up to 700 genes. So it came as quite a shock to researchers from Uppsala University (UU) and their international collaborators that the mutation of just a single gene is responsible for variability in locomotion in horses and mice. Furthermore, the research team discovered that this gene, DMRT3, is expressed in a previously unknown set of neurons in the spinal cord. These findings provide insight into the neural circuits that coordinate movement in vertebrates.
“The amazing result was that we found one very strong signal on one chromosome which by further work led to the discovery of the DMRT3 mutation,” explains Leif Andersson, co-author of the paper published in Nature, from UU and Swedish University of Agricultural Sciences. “This was unexpected since we had [anticipated] a much more complex genetic background for a trait like this.”
Master gene affects neurons that govern breathing at birth and adulthood
When mice are born lacking the master gene Atoh1, none breathe well and all die in the newborn period. Why and how this occurs could provide new answers about sudden infant death syndrome (SIDS), but the solution has remained elusive until now.
Research led by Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital demonstrates that when the gene is lacking in a special population of neurons called RTN (retrotrapezoid nucleus), roughly half the young mice die at birth. Those who survive are less likely to respond to excess levels of carbon dioxide as adults. A report of their work appears online in the journal Neuron.
"The death of mice at birth clued us in that Atoh1 must be needed for the function of some neurons critical for neonatal breathing, so we set out to define these neurons," said Dr. Huda Zoghbi, senior author of the report and director of the Neurological Research Institute and a professor of molecular and human genetics, neuroscience, neurology and pediatrics at BCM. Zoghbi is also a Howard Hughes Medical Institute investigator.
"We took a genetic approach to find the critical neurons," said Wei-Hsiang Huang, a graduate student in the Program in Developmental Biology at BCM who works in Zoghbi’s laboratory. With careful studies to "knockout" the activity of the gene in a narrower and narrower area in the brain, they slowly eliminated possible neurons to determine that loss of Atoh1 in the RTN neurons was the source of the problem.
"Discovering that Atoh1 is indeed critical for the RTN neurons to take their right place in the brainstem and connect with the breathing center helped us uncover why they are important for neonatal breathing," said Zoghbi.
"This population of neurons resides in the ventral brainstem," said Huang. "When there is a change in the makeup of the blood (lack of oxygen or buildup of carbon dioxide), the RTN neurons sense that and tell the body to change the way it breathes." A defect in these neurons can disrupt this response.
"Without Atoh1 the mice have significant breathing problems because they do not automatically adjust their breathing to decrease carbon dioxide and oxygenate the blood," he said.
It turns out the findings from this mouse study are relevant to human studies.
"A paper just published reports that developmental abnormalities in the RTN neurons of children with sudden infant death syndrome or sudden unexplained intrauterine death may be linked to altered ventilatory response to carbon dioxide", said Huang (Lavezzi, A.M., et al., Developmental alterations of the respiratory human retrotrapezoid nucleus in sudden unexplained fetal and infant death, Auton. Neurosci. (2012), doi:10.1016/j.autneu.2012.06.005).
(Source: bcm.edu)
![According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”.
Scientists have long recognised that some non-coding DNA has a function, and more and more solid examples have come to light [edited for clarity - Ed]. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
That the genome is complex will come as no surprise to scientists, but ENCODE does two fresh things: it catalogues the DNA elements for scientists to pore over; and it reveals just how many there are. “The genome is no longer an empty vastness – it is densely packed with peaks and wiggles of biochemical activity,” says Shyam Prabhakar from the Genome Institute of Singapore. “There are nuggets for everyone here. No matter which piece of the genome we happen to be studying in any particular project, we will benefit from looking up the corresponding ENCODE tracks.”](http://41.media.tumblr.com/tumblr_m9y0xaewSN1rog5d1o1_500.jpg)
According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”.
Scientists have long recognised that some non-coding DNA has a function, and more and more solid examples have come to light [edited for clarity - Ed]. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
That the genome is complex will come as no surprise to scientists, but ENCODE does two fresh things: it catalogues the DNA elements for scientists to pore over; and it reveals just how many there are. “The genome is no longer an empty vastness – it is densely packed with peaks and wiggles of biochemical activity,” says Shyam Prabhakar from the Genome Institute of Singapore. “There are nuggets for everyone here. No matter which piece of the genome we happen to be studying in any particular project, we will benefit from looking up the corresponding ENCODE tracks.”
Researchers have discovered two gene variants that raise the risk of the pediatric cancer neuroblastoma. Using automated technology to perform genome-wide association studies on DNA from thousands of subjects, the study broadens understanding of how gene changes may make a child susceptible to this early childhood cancer, as well as causing a tumor to progress.
“We discovered common variants in the HACE1 and LIN28B genes that increase the risk of developing neuroblastoma. For LIN28B, these variants also appear to contribute to the tumor’s progression once it forms,” said first author Sharon J. Diskin, PhD, a pediatric cancer researcher at The Children’s Hospital of Philadelphia. “HACE1 and LIN28B are both known cancer-related genes, but this is the first study to link them to neuroblastoma.”
Diskin and colleagues, including senior author John M. Maris, MD, director of the Center for Childhood Cancer Research at Children’s Hospital, published the study online Sept. 2 in Nature Genetics.
Flying High: Researchers Decipher Manic Gene
ScienceDaily (Sep. 1, 2012) — Flying high, or down in the dumps — individuals suffering from bipolar disorder alternate between depressive and manic episodes. Researchers from the University of Bonn and the Central Institute of Mental Health in Mannheim have now discovered, based on patient data and animal models, how the NCAN gene results in the manic symptoms of bipolar disorder.
(Credit: © Bastos / Fotolia)
The results have been published in the current issue of The American Journal of Psychiatry.
Individuals with bipolar disorder are on an emotional roller coaster. During depressive phases, they suffer from depression, diminished drive and often, also from suicidal thoughts. The manic episodes, however, are characterized by restlessness, euphoria, and delusions of grandeur. The genesis of this disease probably has both hereditary components as well as psychosocial environmental factors.
The NCAN gene plays a major part in how manias manifest
"It has been known that the NCAN gene plays an essential part in bipolar disorder," reports Prof. Dr. Markus M. Nöthen, Director of the Institute of Human Genetics at the University of Bonn. "But until now, the functional connection has not been clear." In a large-scale study, researchers led by the University of Bonn and the Central Institute of Mental Health in Mannheim have now shown how the NCAN gene contributes to the genesis of mania. To do so, they evaluated the genetic data and the related descriptions of symptoms from 1218 patients with differing ratios between the manic and depressive components of bipolar disorder.
Comprehensive data from patients and animal models
Using the patients’ detailed clinical data, the researchers tested statistically which of the symptoms are especially closely related to the NCAN gene. “Here it became obvious that the NCAN gene is very closely and quite specifically correlated with the manic symptoms,” says Prof. Dr. Marcella Rietschel from the Central Institute of Mental Health in Mannheim. According to the data the gene is, however, not responsible for the depressive episodes in bipolar disorder.
Manic mice drank from sugar solution with abandon
A team working with Prof. Dr. Andreas Zimmer, Director of the Institute of Molecular Psychiatry at the University of Bonn, examined the molecular causes effected by the NCAN gene. The researchers studied mice in which the gene had been “knocked out.” “It was shown that these animals had no depressive component in their behaviors, only manic ones,” says Prof. Zimmer. These knockout mice were, e.g., considerably more active than the control group and showed a higher level of risk-taking behavior. In addition, they tended to exhibit increased reward-seeking behavior, which manifested itself by their unrestrained drinking from a sugar solution offered by the researchers.
Lithium therapy also effective against hyperactivity in mice
Finally, the researchers gave the manic knockout mice lithium — a standard therapy for humans. “The lithium dosage completely stopped the animals’ hyperactive behavior,” reports Prof. Zimmer. So the results also matched for lithium; the responses of humans and mice regarding the NCAN gene were practically identical. It has been known from prior studies that knocking out the NCAN gene results in a developmental disorder in the brain due to the fact that the production of the neurocan protein is stopped. “As a consequence of this molecular defect, the individuals affected apparently develop manic symptoms later,” says Prof. Zimmer.
Opportunity for new therapies
Now the scientists want to perform further studies of the molecular connections of this disorder — also with a view towards new therapies. “We were quite surprised to see how closely the findings for mice and the patients correlated,” says Prof. Nöthen. “This level of significance is very rare.” With a view towards mania, the agreement between the findings opens up the opportunity to do further molecular studies on the mouse model, whose results will very likely also be applicable to humans. “This is a great prerequisite for advancing the development of new drugs for mania therapy,” believes Prof. Rietschel.
Source: Science Daily
High quality Denisovan genome sheds light on human evolution: Sequencing our extinct relatives let us know how we differ from chimps.
The discovery that a second branch of the human family shared Asia with our ancestors and the Neanderthals was a real shock, but the Denisovans have continued to surprise many. All we have of them is a bit of a finger and some molars, but those few fragments have yielded a wealth of DNA, and with it the knowledge that the Denisovans interbred with the ancestors of some modern human populations. Now, with the help of a new approach to sequencing ancient DNA, we actually know more about the Denisovans’ genome than we do about Neanderthals’. In the process, we’ve discovered some of the changes that are distinct to modern humans.
Are you addicted to the Internet? You might be able to blame your genes.
Scientists say they’ve found a link between a toxic relationship with the Web and a genetic quirk that also plays a role in nicotine addiction.
Researchers at the University of Bonn in Germany interviewed 843 people about their online habits. Of them, 132 showed signs of an unhealthy relationship with the Internet — all of their thoughts revolved around it and their sense of wellbeing was shaken if they couldn’t go online. By comparing the genes of the two groups, the researchers found the subset of likely Internet addicts more often carried a mutation the CHRNA4 gene, which is typically linked to nicotine addiction.
Expectant mothers are used to fuzzy images on ultrasound monitors and blood tests to screen for potential health problems in their unborn babies. But what if one of those blood tests came back with a readout of the baby’s entire genome? What if a simple test gave parents every nuance of a baby’s genetic makeup before birth?
Recent studies show that it’s possible to decode an entire fetal genome from a sample of the mother’s blood. In the future, doctors may be able to divine a wealth of information about genetic diseases or other characteristics of a fetus from the pregnant mother’s blood. Such tests will raise ethical questions about how to act on such information. But they could also lead to research on treating diseases before birth, and leave parents and their doctors better prepared to care for babies after birth.
One biotech startup wants to restore vision in blind patients with a gene therapy that gives light sensitivity to neurons that don’t normally possess it.
The attempt, by Ann Arbor, Michigan-based Retrosense Therapeutics, will use so-called optogenetics. Scientists have used the technique over the last few years as a research tool to study brain circuits and the neural control of behavior by directing neuron activity with flashes of light. But Retrosense and others groups are pushing to bring the technique to patients in clinical trials.
The idea behind Retrosense’s experimental therapy is to use optogenetics to treat patients who have lost their vision due to retinal degenerative diseases such as retinitis pigmentosa. Patients with retinitis pigmentosa experience progressive and irreversible vision loss because the rods and cones of their eyes die due to an inherited condition. If the company is successful, the treatment could also help patients with the most common form of macular degeneration, which affects nearly a million people in the United States. The U.S. Food and Drug Administration hasn’t approved any therapies for either condition.
The adult human circulatory system contains between 20 and 30 trillion red blood cells (RBCs), the precise size and number of which can vary from person to person. Some people may have fewer, but larger RBCs, while others may have a larger number of smaller RBCs. Although these differences in size and number may seem inconsequential, they raise an important question: Just what controls these characteristics of RBCs?
By analyzing the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells, researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs. Their findings are reported in the September 14 issue of Genes and Development.