Posts tagged genetics
Articles and news from the latest research reports.
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)
In a world of chronic pain, individual treatment possible
An investigation into the molecular causes of a debilitating condition known as “Man on Fire Syndrome” has led Yale researchers to develop a strategy that may lead to personalized pain therapy and predict which chronic pain patients will respond to treatment.
More than a quarter of Americans suffer from chronic pain and nearly 40 percent do not get effective relief from existing drugs. In many common conditions such as diabetic neuropathy, no clear source of pain is found.
The new study published in the Nov. 13 issue of Nature Communications used sophisticated atomic modeling techniques to search for mutations found in a rare, agonizing, and previously untreatable form of chronic pain called erythromelagia, commonly referred to as “Man on Fire Syndrome.” Researchers discovered that one of those mutations seem to predicted whether a patient would respond positively to drug treatment.
“Hopefully we can use this knowledge to help chronic pain patients in more systematic ways, and not depend upon trial and error,” said Yang Yang, postdoctoral research associate in the Department of Neurology and lead author of the paper.
Research suggests that humans are slowly but surely losing intellectual and emotional abilities
Human intelligence and behavior require optimal functioning of a large number of genes, which requires enormous evolutionary pressures to maintain. A provocative hypothesis published in a recent set of Science and Society pieces published in the Cell Press journal Trends in Genetics (1, 2) suggests that we are losing our intellectual and emotional capabilities because the intricate web of genes endowing us with our brain power is particularly susceptible to mutations and that these mutations are not being selected against in our modern society.
"The development of our intellectual abilities and the optimization of thousands of intelligence genes probably occurred in relatively non-verbal, dispersed groups of peoples before our ancestors emerged from Africa," says the papers’ author, Dr. Gerald Crabtree, of Stanford University. In this environment, intelligence was critical for survival, and there was likely to be immense selective pressure acting on the genes required for intellectual development, leading to a peak in human intelligence.
Schizophrenia Genetic Networks Identified; Connection to Autism Found
Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify. In the past few years, researchers have implicated several genes, but it is unclear how they act to produce the disorder. A new study by researchers at Columbia University Medical Center identifies affected gene networks and provides insight into the molecular causes of the disease.
The paper was published in the online edition of the journal Nature Neuroscience.
Using an unbiased collection of hundreds of mutations associated with schizophrenia, the Columbia researchers applied a sophisticated computational approach to uncover hidden relationships among seemingly unrelated genes. The analysis revealed that many of the genes mutated in schizophrenia are organized into two main networks, which take part in a few key processes, including axon guidance, synapse function, neuron mobility, and chromosomal modification.
The study also uncovered an intriguing connection between schizophrenia and autism. “If we hadn’t known that these were two different diseases, and had put all the mutations into a single analysis, it would have come up with very similar networks,” said the study’s senior author, Dennis Vitkup, PhD, associate professor in the Department of Biomedical Informatics, the Center for Computational Biology and Bioinformatics, and the Columbia Initiative in Systems Biology at Columbia University Medical Center. “It shows how closely the autism and schizophrenia genetic networks are intertwined,” he added.
Extra chromosome 21 removed from Down syndrome cell line
University of Washington scientists have succeeded in removing the extra copy of chromosome 21 in cell cultures derived from a person with Down syndrome, a condition in which the body’s cells contain three copies of chromosome 21 rather than the usual pair.
A triplicate of any chromosome is a serious genetic abnormality called a trisomy. Trisomies account for almost one-quarter of pregnancy loss from spontaneous miscarriages, according to the research team. Besides Down syndrome (trisomy 21), some other human trisomies are extra Y or X chromosomes, and Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), both of which have extremely high newborn fatality rates.
In their report appearing in the Nov. 2 edition of Cell Stem Cell, a team led by Dr. Li B. Li of the UW Department of Medicine described how they corrected trisomy 21 in human cell lines they grew in the lab. The senior scientists on the project were gene therapy researchers Dr. David W. Russell, professor of medicine and biochemistry, and Dr. Thalia Papayannopoulou, professor of medicine.
The targeted removal of a human trisomy, they noted, could have both clinical and research applications.
New, Improved Mouse Model of Human Alzheimer’s May Enable Drug Discovery
Researchers at the University of Illinois at Chicago College of Medicine have developed a transgenic mouse that carries a human gene known to increase risk of Alzheimer’s 15-fold. This new mouse mimics the genetics of the human disease more closely than any of the dozen existing mouse models and may prove more useful in the development of candidate drugs to prevent or treat the disease.
The new mouse model provides new evidence for the earliest cause of Alzheimer’s, researchers report in a study to be published in the December issue of the Journal of Biological Chemistry and now available online.
The model is a cross between an existing transgenic Alzheimer’s mouse and a mouse carrying fully human apoE, a gene that in one of its three variants, apoE4, is the greatest genetic risk factor for Alzheimer’s in the human population.
(Source: tigger.uic.edu)
Scripps Florida Scientists Uncover Secrets of How Intellect and Behavior Emerge During Childhood
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a single protein plays an oversized role in intellectual and behavioral development. The scientists found that mutations in a single gene, which is known to cause intellectual disability and increase the risk of developing autism spectrum disorder, severely disrupts the organization of developing brain circuits during early childhood. This study helps explain how genetic mutations can cause profound cognitive and behavioral problems.
The study was published in the November 9, 2012, issue of the journal Cell.
The genetic mutations that cause developmental disorders, such as intellectual disability and autism spectrum disorder, commonly affect synapses, the junctions between two nerve cells that are part of the brain’s complex electro-chemical signaling system. A substantial percentage of children with severe intellectual and behavioral impairments are believed to harbor single mutations in critical neurodevelopmental genes. Until this study, however, it was unclear precisely how pathogenic genetic mutations and synapse function were related to the failure to develop normal intellect.
“In this study, we did something no one else had done before,” said Gavin Rumbaugh, a TSRI associate professor who led the new research. “Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder.”
Humans, Chimpanzees and Monkeys Share DNA but Not Gene Regulatory Mechanisms
Humans share over 90% of their DNA with their primate cousins. The expression or activity patterns of genes differ across species in ways that help explain each species’ distinct biology and behavior.
DNA factors that contribute to the differences were described on Nov. 6 at the American Society of Human Genetics 2012 meeting in a presentation by Yoav Gilad, Ph.D., associate professor of human genetics at the University of Chicago.
Dr. Gilad reported that up to 40% of the differences in the expression or activity patterns of genes between humans, chimpanzees and rhesus monkeys can be explained by regulatory mechanisms that determine whether and how a gene’s recipe for a protein is transcribed to the RNA molecule that carries the recipe instructions to the sites in cells where proteins are manufactured.
In addition to improving scientific understanding of the uniqueness of humans, studies such as the investigation conducted by Dr. Gilad and colleagues could have relevance to human health and disease.
"Through inter-species’ comparisons at the DNA sequence and expression levels, we hope to identify the genetic basis of human specific traits and in particular the genetic variations underlying the higher susceptibility to certain diseases such as malaria and cancer in humans than in non-human primates," said Dr. Gilad.
Dr. Gilad and his colleagues studied gene expression in lymphoblastoid cell lines, laboratory cultures of immortalized white blood cells, from eight humans, eight chimpanzees and eight rhesus monkeys.
They found that the distinct gene expression patterns of the three species can be explained by corresponding changes in genetic and epigenetic regulatory mechanisms that determine when and how a gene’s DNA code is transcribed to a messenger RNA (mRNA) molecule.
Dr. Gilad also determined that the epigenetics process known as histone modification also differs in the three species. The presence of histone marks during gene transcription indicates that the process is being prevented or modified.
"These data allowed us to identify both conserved and species-specific enhancer and repressor regulatory elements, as well as characterize similarities and differences across species in transcription factor binding to these regulatory elements," Dr. Gilad said.
Among the similarities among the three species were the promoter regions of DNA that initiated transcription of a particular gene.
In all three species, Dr. Gilad’s lab found that transcription factor binding and histone modifications were identical in over 67% of regulatory elements in DNA segments that are regarded as promoter regions.
The researchers presentation is titled, “Genome-wide comparison of genetic and epigenetic regulatory mechanisms in primates.”
(Source: sciencedaily.com)
Low vitamin D levels associated with longevity
Low levels of vitamin D may be associated with longevity, according to a study involving middle-aged children of people in their 90s published in CMAJ (Canadian Medical Association Journal).
"We found that familial longevity was associated with lower levels of vitamin D and a lower frequency of allelic variation in the CYP2R1 gene, which was associated with higher levels of vitamin D," writes Dr. Diana van Heemst, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands, with coauthors.
Previous studies have shown that low levels of vitamin D are associated with increased rates of death, heart disease, diabetes, cancer, allergies, mental illness and other afflictions. However, it is not known whether low levels are the cause of these diseases or if they are a consequence.
To determine whether there was an association between vitamin D levels and longevity, Dutch researchers looked at data from 380 white families with at least 2 siblings over age 90 (89 years or older for men and 91 year or older for women) in the Leiden Longevity Study. The study involved the siblings, their offspring and their offsprings’ partners for a total of 1038 offspring and 461 controls. The children of the nonagenarians were included because it is difficult to include controls for the older age group. The partners were included because they were of a similar age and shared similar environmental factors that might influence vitamin D levels.
The researchers measured levels of 25(OH) vitamin D and categorized levels by month as they varied according to season. Tanning bed use, which can affect vitamin D levels, was categorized as never, 1 times per year and 6 times per year. The researchers controlled for age, sex, BMI (body mass index), time of year, vitamin supplementation and kidney function, all factors that can influence vitamin D levels. They also looked at the influence of genetic variation in 3 genes associated with vitamin D levels.
"We found that the offspring of nonagenarians who had at least 1 nonagenarian sibling had lower levels of vitamin D than controls, independent of possible confounding factors and SNPs [single nucleotide polymorphisms] associated with vitamin D levels," write the authors. "We also found that the offspring had a lower frequency of common genetic variants in the CYP2R1 gene; a common genetic variant of this gene predisposes people to high vitamin D levels.
These findings support an association between low vitamin D levels and familial longevity.” They postulate that offspring of nonagenarians might have more of a protein that is hypothesized to be an “aging suppressor” protein. More research is needed to understand the link between lower vitamin D levels, genetic variants and familial longevity.
(Source: eurekalert.org)
Inflammation and Cognition in Schizophrenia
There are a growing number of clues that immune and inflammatory mechanisms are important for the biology of schizophrenia. In a new study in Biological Psychiatry, Dr. Mar Fatjó-Vilas and colleagues explored the impact of the interleukin-1β gene (IL1β) on brain function alterations associated with schizophrenia.
Fatjó-Vilas said that “this study is a contribution to the relatively new field of ‘functional imaging genetics’ which appears to be potentially powerful for the study of schizophrenia, where genetic factors are of established importance and cognitive impairment – affecting particularly executive function and long-term memory – is increasingly recognized as a core feature of the disorder.”
To conduct this study, they recruited patients with schizophrenia and healthy volunteers, all of whom completed a working memory task while undergoing a functional magnetic resonance imaging scan in the laboratory. This allowed the researchers to determine which areas of the brain became activated during the task. Each participant was also genotyped to determine which allelic combination of the -511C/T polymorphism at the promoter region of the IL1β gene they carry: CC, TT, or CT.
Patients who were homozygous for the C allele (CC) showed reduced prefrontal cortex activation associated with working memory than patients who had at least one copy of the T allele. Among the healthy volunteers, frontal brain activation did not differ according to genotype.
“The analyzed genetic variant exerts an influence on prefrontal cortex function and this influence is different in healthy subjects and patients with schizophrenia,” summarized Fatjó-Vilas.
An important issue is that the -511C/T seems to have a role in regulating the levels of IL1B expression, in which case it would influence neuronal activity dependent on the protein availability. This means that the T allele has been reported to be more active than the C allele, suggesting that a tendency for greater expression of IL1β is associated with greater compromise of frontal cortical functions underlying cognition.
Interleukin-1β is released in the blood under stressful conditions and its release is one of the ways that stress promotes inflammation. IL-1β levels in the blood are altered, for example, in patients with depression and other neuropsychiatric disorders.
Apart from having a role in the immune system, interleukins are also involved in a variety of developmental and functioning processes of the central nervous system. Thus, this study provides further clues for identifying specific biological mechanisms of the disorder associated with both neurodevelopmental processes and immunological and stress response functions.
Dr. John Krystal, Editor of Biological Psychiatry, commented, “We are just beginning to explore the functional impact of inflammatory mechanisms in schizophrenia and the current findings increase our curiosity about these novel mechanisms.”
(Source: alphagalileo.org)