gene-mutations

the-green-anon  asked:

Examine! Shiny Pokemon.

rpg item meme | @the-green-anon

 You recognize this term as slang for the pokémon with gene mutations that result in their unusual color. It’s not a focus of study for you, because the fad already has more attention than it needs. You wish there were more ways to sway trainers from requesting these ‘glorified’ pokémon, and for breeders to stop trying to supply the demand. All pokémon have intrinsic worth - it’s the inside that counts the most - not the outside. 

The idea of people treating living beings as mere accessories breaks your heart.

Study suggests potential therapy for second most common form of dementia

Drugs that boost the function of a specific type of neurotransmitter receptor may provide benefit to patients with the second most common type of dementia, according to research by scientists at the University of Alabama at Birmingham published today in the Journal of Neuroscience.

Frontotemporal dementia, known as FTD, is a devastating disease in which patients have rapid and dramatic changes in behavior, personality and social skills. The age of onset for FTD is relatively young, usually striking patients in their mid- to late 50s. The prognosis is grim; patients quickly deteriorate and usually die within 10 years after onset. Currently, there is no effective treatment for FTD.

The UAB research team’s effort focused on mutations in certain genes, primarily in the Microtubule Associated Protein Tau gene. An accumulation of tau protein is associated with Alzheimer’s disease, the most common form of dementia; but little is known how tau mutations affect specific brain regions and cause FTD.

The UAB researchers used a new mouse model expressing human tau with an FTD-associated mutation. These mice demonstrate physical behaviors similar to those seen in humans with FTD — compulsive, excessively repetitive actions such as grooming, for example. The mice also had impaired synaptic and network function in certain brain network regions.

“We found that mutant tau impairs synapses — the connections between neurons — by reducing the size of the anchoring sites of an essential glutamate receptor called NMDA,” said Erik Roberson, M.D., Ph.D., associate professor in the Department of Neurology and primary investigator for the study. “Reduction of the anchoring sites left fewer NMDA receptors available at the synapse to receive excitatory signals, thus limiting synaptic firing and network activity.”

The team then employed cycloserine, a drug already approved for use by the FDA, which is known to assist NMDA receptor function. This boost of NMDA receptor function was able to restore synaptic firing and thereby restore network activity in the animal model. The restoration of normal network activity reversed the behavioral abnormalities seen in the mice.

“This study provides mechanistic insight into how a tau mutation affects specific brain regions to impair a network,” said Roberson. “It also provides a potential therapeutic target, the NMDA receptor, which appears to correct the network and behavioral abnormalities.”

Roberson’s team hypothesizes that increasing NMDA receptor function may benefit human FTD patients. With further preclinical validation, this hypothesis could be tested in clinical trials using the already available drug cycloserine.

False-colored scanning electron micrograph of human embryonic stem cell (gold) growing within a cradling cluster of supporting fibroblasts. Image courtesy of Annie Cavanaugh, Wellcome Images

The trouble within stem cells

Inducing human pluripotent stem cells to become any kind of desired cell has the potential to transform medicine: Doctors could, for example, repair, rebuild – maybe even build anew – damaged or diseased organs.

Of course, nature has had millions of years to master the process – and it doesn’t often even attempt things like regeneration. Humans are strictly rank beginners, still struggling to fully understand the countless complexities of biological construction and overcome the myriad obstacles to success.

Chief among them is the concern that induced stem cells might carry or create mutations that, in the process of differentiation and growth, would introduce or exacerbate disease, rather than cure it. A 2011 paper published in Nature by Kun Zhang, PhD, at UC San Diego, for example, found that genetic material of reprogrammed cells may in fact be compromised.

Nowhere is this more worrisome than in efforts to find stem cell-based therapies to treat cancer, which is essentially a disease of gene mutations. The greater the “mutational load,” the greater the chance of cancer.

In a new paper, published in the journal Cell Reports, Louise Laurant, MD, PhD, adjunct assistant professor in the Department of Reproductive Medicine at UC San Diego School of Medicine, and colleagues describe analyses of two sets of human embryonic stem cell (hESC) lines.

They showed for the first time that different genetic aberrations tend to occur at different stages of development in hESCs. During preimplantation embryo development and early derivation, mutations are mainly deletions or “loss of heterozygosity,” which occurs when some copies of primary nucleobases (cytosine, guanine, adenine, thymine and uracil) are missing.

Conversely, long-term culturing of hESCs aberrations are more frequently duplications of genetic information.

The findings reinforce the importance and need to measure and monitor the genetic integrity of hESCs, and specifically point to areas of concern.

Serious efforts are being made in this regard. For example, Steven Dowdy, PhD, professor in the UC San Diego Department of Cellular & Molecular Medicine, recently published a paper describing a simple, easy RNA-based method of generating human induced pluripotent stem cells. You can read the news release here.

How do mutations in genes result in red-green color blindness? Approximately 8% of males are red-green colorblind, and while the condition can be inconvenient, it is not life-threatening and most learn to adjust at an early age.

Image: Example of an Ishihara color test plate. Creator unknown. Public domain via Wikimedia Commons.

Examples of Gene Mutations

Cystic Fibrosis
ΔF508 mutation accounts for 70% of mutations in Caucasian populations, mutation is deletion of 3 bases in DNA coding
There are currently 1913 mutations listed for CF in the database including:
nonsense, missense, frameshift, insertion/deletion, splicing 

beta-Thalassaemia
Missense mutants – changes amino acid
Nonsense mutants - introduces stop codon
Frameshift mutants - e.g. deletion of 2 bases at codon 8 
Splicing mutants - Single nucleotide changes create new splice site, extended exon 2 

Huntington Disease

  • Defect in gene is a triplet (3 base) repeat (CAG) <35 repeats normal (most 17-20)
  • 27-35 rare but unstable when transmitted via a male
  • 36 - 41 indeterminate (reduced penetrance)
  • 40-50 most adult cases
  • >50 generally juvenile onset
  • Earlier onset and more severe if inherited from father 

Link seen between seizures and migraines in the brain

Seizures and migraines have always been considered separate physiological events in the brain, but now a team of engineers and neuroscientists looking at the brain from a physics viewpoint discovered a link between these and related phenomena.

Scientists believed these two brain events were separate phenomena because they outwardly affect people very differently. Seizures are marked by electrical hyperactivity, but migraine auras – based on an underlying process called spreading depression – are marked by a silencing of electrical activity in part of the brain. Also, seizures spread rapidly, while migraines propagate slowly.

“We wanted to make a more realistic model of what underlies migraines, which we were working on controlling,” said Steven J. Schiff, Brush Chair Professor of Engineering and director of the Penn State Center for Neural Engineering. “We realized that no one had ever kept proper track of the neuronal energy being used and all of the ions, the charged atoms, going into and out of brain cells.”

Potassium and sodium contribute the ions that control electricity in the brain. The Penn State researchers added fundamental physics principles of conservation of energy, charge and mass to an older theory of this electricity. They kept track of the energy required to run a nerve cell, and kept count of the ions passing into and out of the cells.

The brain needs a constant supply of oxygen to keep everything running because it has to keep pumping the ions back across cell membranes after each electrical spike. The energy supply is directly linked to oxygen concentrations around the cell and the energy required to restore the ions to their proper places is much greater after seizures or migraines.

“We know that some people get both seizures and migraines,” said Schiff. “Certainly, the same brain cells produce these different events and we now have increasing numbers of examples of where single gene mutations can produce the presence of both seizure and migraines in the same patients and families. So, in retrospect, the link was obvious – but we did not understand it.”

The researchers, who also included Yina Wei, recent Penn State Ph.D. in engineering science and mechanics, currently a postdoctoral fellow at University of California-Riverside, and Ghanim Ullah, former Penn State postdoctoral fellow, now a professor of physics at University of South Florida, explored extending older models of brain cell activity with basic conservation principles. They were motivated by previous Penn State experiments that showed the very sensitive link between oxygen concentration with reliable and rapid changes in nerve cell behavior.

What they found was completely unexpected. Adding basic conservation principles to the older models immediately demonstrated that spikes, seizures and spreading depression were all part of a spectrum of nerve cell behavior. It appeared that decades of observations of different phenomena in the brain could share a common underlying link.

“We have found within a single model of the biophysics of neuronal membranes that we can account for a broad range of experimental observations, from spikes to seizures and spreading depression,” the researchers report in a recent issue of the Journal of Neuroscience. “We are particularly struck by the apparent unification possible between the dynamics of seizures and spreading depression.”

While the initial intent was to better model the biophysics of the brain, the connection and unification of seizures and spreading depression was an emergent property of that model, according to Schiff.

“No one, neither us nor our colleagues anticipated such a finding or we would have done this years ago,” said Schiff. “But we immediately recognized what the results were showing and we worked intensively to test the integrity of this result in many ways and we found out how robust it was. Although the mathematics are complex, the linking of these phenomena seems rock solid.”

The ability to better understand the difference between normal and pathological activity within the brain may lead to the ability to predict when a seizure might occur.

“We are not only interested in controlling seizures or migraines after they begin, but we are keen to seek ways to stabilize the brain in normal operating regimes and prevent such phenomena from occurring in the first place,” said Schiff. “This type of unification framework demonstrates that we can now begin to have a much more fundamental understanding of how normal and pathological brain activities relate to each other. We and our colleagues have a lot on our plate to start exploring over the coming years as we build on this finding.”

(Image caption: Alterations of the human 16p11.2 chromosomal region lead to a variety of cognitive disorders, including autism. Credit: Pasieka/Science Source)

New findings reveal genetic brain disorders converge at the synapse

Several genetic disorders cause intellectual disability and autism. Historically, these genetic brain diseases were viewed as untreatable. However, in recent years neuroscientists have shown in animal models that it is possible to reverse the debilitating effects of these gene mutations. But the question remained whether different gene mutations disrupt common physiological processes. If this were the case, a treatment developed for one genetic cause of autism and intellectual disability might be useful for many others.

In a paper published today in the online edition of Nature Neuroscience, a research team led by Mark Bear, the Picower Professor of Neuroscience in MIT’s Picower Institute for Learning and Memory, showed that two very different genetic causes of autism and intellectual disability disrupt protein synthesis at synapses, and that a treatment developed for one disease produced a cognitive benefit in the other. The research was performed by postdoc and lead author Di Tian, graduate student Laura Stoppel, and research scientist Arnold Heynen, in collaboration with scientists at Cold Spring Harbor Laboratory and Roche Pharmaceuticals.

Researching the role of fragile X syndrome

One heritable cause of intellectual disability and autism is fragile X syndrome, which arises when a single gene on the X chromosome, called FMR1, is turned off during brain development. Fragile X is rare, affecting one in about 4,000 individuals. In previous studies using mouse models of fragile X, Bear and others discovered that the loss of this gene results in exaggerated protein synthesis at synapses, the specialized sites of communication between neurons.

Of particular interest, they found that this protein synthesis was stimulated by the neurotransmitter glutamate, downstream of a glutamate receptor called mGluR5. This insight led to the idea, called the mGluR theory, that too much protein synthesis downstream of mGluR5 activation gives rise to many of the psychiatric and neurological symptoms of fragile X. Bear’s lab tested this idea in mice, and found that inhibiting mGluR5 restored balanced protein synthesis and reversed many defects in the animal models.

Different genes, same consequences

Another cause of autism and intellectual disability is the loss of a series of genes on human chromosome 16, called a 16p11.2 microdeletion. Some of the 27 affected genes play a role in protein synthesis regulation, leading Bear and colleagues to wonder if 16p11.2 microdeletion syndrome and fragile X syndrome affect synapses in the same way. To address this question, the researchers used a mouse model of 16p11.2 microdeletion, created by Alea Mills at Cold Spring Harbor Laboratory. 

Using electrophysiological, biochemical, and behavioral analyses, the MIT team compared this 16p11.2 mouse with what they already had established in the fragile X mouse. Synaptic protein synthesis was indeed disrupted in the hippocampus, a part of the brain important for memory formation. Moreover, when they tested memory in these mice, they discovered a severe deficit, similar to fragile X.

Restoring brain function after disease onset

These findings encouraged the MIT researchers to attempt to improve memory function in the 16p11.2 mice with the same approach that has worked in fragile X mice. Treatment with an mGluR5 inhibitor, provided by a team of scientists at Roche led by Lothar Lindemann, substantially improved cognition in these mice. Of particular importance, this benefit was achieved with one month of treatment that began well after birth. The implication, according to Bear, is that “some cognitive aspects of this disease, previously believed to be an intractable consequence of altered early brain development, might instead arise from ongoing alterations in synaptic signaling that can be corrected by drugs.”

Current research indicates that well over 100 distinct gene mutations can manifest as intellectual disability and autism. The current findings are heartening, as they indicate not only that drug therapies might be effective to improve cognition and behavior in affected individuals, but also that a treatment developed for one genetic cause might apply more broadly to many others.

Dozens of Genes Associated with Autism in New Research

Two major genetic studies of autism, led in part by UC San Francisco scientists and involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows that rare mutations in these genes affect communication networks in the brain and compromise fundamental biological mechanisms that govern whether, when, and how genes are activated overall.

The two new studies, published in the advance online edition of Nature (1, 2) on October 29, 2014, tied mutations in more than 100 genes to autism. Sixty of these genes met a “high-confidence” threshold indicating that there is a greater than 90 percent chance that mutations in those genes contribute to autism risk.

The majority of the mutations identified in the new studies are de novo (Latin for “afresh”) mutations, meaning they are not present in unaffected parents’ genomes but arise spontaneously in a single sperm or egg cell just prior to conception of a child.

The genes implicated in the new studies fall into three broad classes: they are involved in the formation and function of synapses, which are sites of nerve-cell communication in the brain; they regulate, via a process called transcription, how the instructions in other genes are relayed to the protein-making machinery in cells; and they affect how DNA is wound up and packed into cells in a structure known as chromatin. Because modifications of chromatin structure are known to lead to changes in how genes are expressed, mutations that alter chromatin, like those that affect transcription, would be expected to affect the activity of many genes.

One of the new Nature studies made use of data from the Simons Simplex Collection (SSC), a permanent repository of DNA samples from nearly 3,000 families created by the Simons Foundation Autism Research Initiative. Each SSC family has one child affected with autism, parents unaffected by the disorder and, in a large proportion, unaffected siblings. The second study was conducted under the auspices of the Autism Sequencing Consortium (ASC), an initiative supported by the National Institute of Mental Health that allows scientists from around the world to collaborate on large genomic studies that couldn’t be done by individual labs.

“Before these studies, only 11 autism genes had been identified with high confidence, and we have now more than quadrupled that number,” said Stephan Sanders, PhD, assistant professor of psychiatry at UCSF, co-first author on the SSC study, and co-author on the ASC study. Based on recent trends, Sanders estimates that gene discovery will continue at a quickening pace, with as many as 1,000 genes ultimately associated with autism risk.

“There has been a lot of concern that 1,000 genes means 1,000 different treatments, but I think the news is much brighter than that,” said Matthew W. State, MD, PhD, chair and Oberndorf Family Distinguished Professor in Psychiatry at UCSF. State was co-leader of the Nature study focusing on the SSC and a senior participant in the study organized by the ASC, of which he is a co-founder. ”There is already strong evidence that these mutations converge on a much smaller number key biological functions. We now need to focus on these points of convergence to begin to develop novel treatments.

Autism, which is marked by deficits in social interaction and language development, as well as by repetitive behaviors and restricted interests, is known to have a strong genetic component. But until a few years ago, genomic research had failed to decisively associate individual genes with the disorder.

The two new studies highlight the factors that have radically changed that picture, State said. One is the advent of next-generation sequencing (NGS), which allows researchers to read each of the “letters” in the DNA code at unprecedented speed. Another is the establishment of the SSC; a 2007 study had suggested that de novo mutations would play a significant role in autism risk, and the SSC was specifically designed to help test that idea by allowing for close comparisons between children with autism and their unaffected parents and siblings. Lastly, collaborative initiatives such as the ASC are enabling teams of researchers around the world to work closely together, pooling their resources to create large datasets with sufficient statistical power to draw valid conclusions.

The large research teams behind each of the two new studies used a form of NGS known as “whole-exome” sequencing, a letter-by-letter analysis of just the portion of the genome that encodes proteins.

In November 2013, a study led by A. Jeremy Willsey, a graduate student in State’s lab, showed that the functional roles of the nine high-confidence autism risk genes that had then been discovered all converged on a single cell type in a particular place in the brain at a particular time during fetal development. Willsey is a co-author on both of the new Nature studies, which State believes will further accelerate our understanding of how the myriad of genes involved in autism affect basic biological pathways in the brain.

“These genes carry really large effects,” State said. “That we now have a bounty of dozens of genes, and a clear path forward to find perhaps hundreds more, provides an incredible foundation for understanding the biology of autism and finding new treatments.”

Overhaul of our understanding of why autism potentially occurs

An analysis of autism research covering genetics, brain imaging, and cognition led by Laurent Mottron of the University of Montreal has overhauled our understanding of why autism potentially occurs, develops and results in a diversity of symptoms. The team of senior academics involved in the project calls it the “Trigger-Threshold-Target’’ model. Brain plasticity refers to the brain’s ability to respond and remodel itself, and this model is based on the idea that autism is a genetically induced plastic reaction. The trigger is multiple brain plasticity-enhancing genetic mutations that may or may not combine with a lowered genetic threshold for brain plasticity to produce either intellectual disability alone, autism, or autism without intellectual disability. The model confirms that the autistic brain develops with enhanced processing of certain types of information, which results in the brain searching for materials that possess the qualities it prefers and neglecting materials that don’t. “One of the consequences of our new model will be to focus early childhood intervention on developing the particular strengths of the child’s brain, rather than exclusively trying to correct missing behaviors, a practice that may be a waste of a once in a lifetime opportunity,” Mottron said.

Mottron and his colleagues developed the model by examining the effect of mutations involved in autism together with the brain activity of autistic people as they undertake perceptual tasks. “Geneticists, using animals implanted with the mutations involved in autism, have found that most of them enhance synaptic plasticity – the capacity of brain cells to create connections when new information is encountered. In parallel, our group and others have established that autism represents an altered balance between the processing of social and non-social information, i.e. the interest, performance and brain activity, in favor of non-social information,” Mottron explained. “The Trigger-Threshold-Target model builds a bridge between these two series of facts, using the neuro cognitive effects of sensory deprivation to resolve the missing link between them.”

The various superiorities that subgroups of autistic people present in perception or in language indicates that an autistic infant’s brain adapts to the information it is given in a strikingly similar way to sensory-deprived people. A blind infant’s brain compensate the lack of visual input by developing enhanced auditory processing abilities for example, and a deaf infant readapts to process visual inputs in a more refined fashion. Similarly, cognitive and brain imaging studies of autistic people work reveal enhanced activity, connectivity and structural modifications in the perceptive areas of the brain. Differences in the domain of information “targeted’’ by these plastic processes are associated with the particular pattern of strengths and weaknesses of each autistic individual. “Speech and social impairment in some autistic toddlers may not be the result of a primary brain dysfunction of the mechanisms related to these abilities, but the result of their early neglect,” Mottron said. “Our model suggests that the autistic superior perceptual processing compete with speech learning because neural resources are oriented towards the perceptual dimensions of language, neglecting its linguistic dimensions. Alternatively, for other subgroups of autistic people, known as Asperger, it’s speech that’s overdeveloped. In both cases, the overdeveloped function outcompetes social cognition for brain resources, resulting in a late development of social skills.”

The model provides insight into the presence or absence of intellectual disability, which when causative mutation alter the function of brain cell networking. Rather than simply triggering a normal but enhanced plastic reaction, these mutations cause neurons to connect in a way that does not exist in non-autistic people. When brain cell networking functions normally, only the allocation of brain resources is changed.

As is the case with all children, environment and stimulation have an effect on the development and organization of an autistic child’s brain. “Most early intervention programs adopt a restorative approach by working on aspects like social interest. However this focus may monopolize resources in favor of material that the child process with more difficulties, Mottron said. “We believe that early intervention for autistic children should take inspiration from the experience of congenitally deaf children, whose early exposure to sign language has a hugely positive effect on their language abilities. Interventions should therefore focus on identifying and harnessing the autistic child’s strengths, like written language.” By indicating that autistic ‘'restricted interests’’ result from cerebral plasticity, this model suggest that they have an adaptive value and should therefore be the focus of intervention strategies for autism.

Genetic legacy from the Ottoman Empire: Single mutation causes rare brain disorder

An international team of researchers have identified a previously unknown neurodegenerative disorder and discovered it is caused by a single mutation in one individual born during the height of the Ottoman Empire in Turkey about 16 generations ago.

(Image caption: An fMRI scan of the brain of a patient with CLP1 mutation reveals severe atrophy of the brainstem (red line) and cerebellum (blue) as well as lack of formation of the corpus callosum (green), which connects both sides of the cerebrum (yellow), which is also atrophied. The lines outline approximately the expected sizes of the brain areas. A study traced the mutation to a single individual born in Turkey during the Ottoman Empire, some 16 generations ago.)

The genetic cause of the rare disorder was discovered during a massive analysis of the individual genomes of thousands of Turkish children suffering from neurological disorders.

“The more we learn about basic mechanisms behind rare forms of neuro-degeneration, the more novel insights we can gain into more common diseases such as Alzheimer’s or Lou Gehrig’s Disease,” said Murat Gunel, the Nixdorff-German Professor of Neurosurgery, and professor of genetics and neurobiology at Yale.

Gunel is a senior co-author of one of two papers published in the April 24 issue of the journal Cell that document the devastating effects of a mutation in the CLP1 gene. Gunel and colleagues at Yale Center for Mendelian Genomics along with Joseph Gleeson’s group at University of California-San Diego compared DNA sequencing results of more than 2,000 children from different families with neurodevelopmental disorders. In four apparently unrelated families, they identified the exact same mutation in the CLP1 gene. Working with the Frank Bass group from the Netherlands, the researchers also studied how CLP1 mutations interfered with the transfer of information encoded within genes to cells’ protein-making machinery.

The discovery of the identical mutation in seemingly unrelated families originally from eastern Turkey suggested an ancestral mutation, dating back several generations, noted the researchers.

Affected children suffer from intellectual disability, seizures, and delayed or absent mental and motor development, and their imaging studies show atrophy affecting the cerebral cortex, cerebellum, and the brain stem.

The second Cell paper by researchers from Baylor School of Medicine and Austria also found the identical founder mutation in CLP1 in another 11 children from an additional five families originally from eastern Turkey.

Gunel said that the high prevalence of consanguineous marriages [between closely related people] in Turkey and the Middle East leads to these rare recessive genetic neurodegenerative disorders. Affected children inherit mutations in the same gene from both of their parents, who are closely related to each other, such as first cousins. Without consanguinity between parents, children are very unlikely to inherit two mutations in the same gene.

“By dissecting the genetic basis of these neurodevelopmental disorders, we are gaining fundamental insight into basic physiological mechanisms important for human brain development and function” Gunel said. “We learn a lot about normal biology by studying what happens when things go wrong.”

Environmental Influences May Cause Autism in Some Cases

Research by scientists at Albert Einstein College of Medicine of Yeshiva University may help explain how some cases of autism spectrum disorder (ASD) can result from environmental influences rather than gene mutations. The findings, published online today in PLOS Genetics, shed light on why older mothers are at increased risk for having children with ASD and could pave the way for more research into the role of environment on ASD.

The U.S. Centers for Disease Control and Prevention announced in March that one in 68 U.S. children has an ASD—a 30 percent rise from 1 in 88 two years ago. A significant number of people with an ASD have gene mutations that are responsible for their condition. But a number of studies—particularly those involving identical twins, in which one twin has ASD and the other does not—show that not all ASD cases arise from mutations.

In fact, a major study of more than 14,000 children with ASDs published earlier this month in the Journal of the American Medical Association concluded that gene abnormalities could explain only half the risk for developing ASD. The other half of the risk was attributable to “nongenetic influences,” meaning environmental factors that could include the conditions in the womb or a pregnant woman’s stress level or diet. 

Keep reading

How Postsynaptic Density Forms and Why Defects Can Cause Autism

All neurons in our brain are wired via a micron-sized connection unit called synapse, and each synapse contains a layer of densely-packed, protein rich compartment called postsynaptic density (PSD), which is responsible for brain signal processing and transmission. Mutations of genes encoding PSD proteins are major causes of psychiatric disorders including autisms, schizophrenia, and intellectual disabilities (ID). While the existence of PSDs has been known to scientists for 60 years, how PSDs form and change in response to brain activities are poorly understood.

The research will appear in Cell.

Image JD4230 (Tay-Sachs Disease, illustration)

An illustration of Tay-Sachs disease, a rare, inherited disorder that progressively destroys neurons in the brain. 

Tay-Sachs is most commonly seen during infancy as development begins to slow and muscles begin to weaken. Fatty substances in the brain, known as GM2 gangliosides (green), are used as an energy source but become toxic in large concentrations.

SEE HUMAN NEURON ILLUSTRATIONS

Children affected by Tay-Sachs lack a lysosomal enzyme necessary to break down these fat molecules, due to a mutated gene. The disease eventually progesses into seizures, vision and hearing loss, intellectual disability, and paralysis as more neurons absorb these toxic fats without the ability to break them down. As a result, most infants only live until early childhood.

© Evan Oto / Science Source

Researcher discovers two new genes linked to intellectual disability

Researchers at the Centre for Addiction and Mental Health have discovered two new genes linked to intellectual disability, according to two research studies published concurrently in early March in the journals Human Genetics and Human Molecular Genetics.

“Both studies give clues to the different pathways involved in normal neurodevelopment,” says CAMH Senior Scientist Dr. John Vincent, who heads the MiND (Molecular Neuropsychiatry and Development) Laboratory in the Campbell Family Mental Health Research Institute at CAMH. “We are building up a body of knowledge that is informing us which kinds of genes are important to, and involved in, intellectual disabilities.”

In the first study, Dr. Vincent and his team used microarray genotyping to map the genes of a large consanguineous (intermarriage within the extended family) Pakistani family, in which five members of the youngest generation were affected with mild to moderate intellectual disability. Dr. Vincent identified a truncation in the FBXO31 gene, which plays a role in the way that proteins are processed during neuronal development, particularly in the cerebellar cortex.

In the second study, using the same techniques, Dr. Vincent and his team analyzed the genes of two consanguineous families, one Austrian and one Pakistani, and identified a disruption in the METTL23 gene linked to mild recessive intellectual disability. The METTL23 gene is involved in methylation—a process important to brain development and function.

About one per cent of children worldwide are affected by non-syndromic (i.e., the absence of any other clinical features) intellectual disability, a condition characterized by an impaired capacity to learn and process new or complex information, leading to decreased cognitive functioning and social adjustment. Although trauma, infection and external damage to the unborn fetus can lead to an intellectual disability, genetic defects are a principal cause.

These studies were part of an ongoing study of affected families in Pakistan, where the cultural tradition of large families and consanguineous marriages among first cousins increases the likelihood of inherited intellectual disability in offspring.

“Although it is easier to find and track genes in consanguineous families, these genes are certainly not limited to them,” Dr. Vincent points out. A recent study estimated that 13–24 per cent of intellectual disability cases among individuals of European descent have autosomal recessive causes, meaning that results of this study are very relevant to populations such as Canada.

Autosomal recessive gene mutations have traditionally been more difficult to trace, resulting in a paucity of research in this area. Parents of affected children show no symptoms, and the child must inherit one defective copy of the gene from each parent, so that only one in four offspring are likely to be affected. Smaller families, therefore, show a decreased incidence and are less amenable to this kind of study.

Dr. Vincent is currently engaged in a study that will screen Canadian populations with autism and intellectual disability for autosomal recessive gene mutations. Results will be available later this year.

A total of 42 genes linked to non-syndromic autosomal recessive forms of intellectual disability have now been identified; estimates suggest that up to 2,500 autosomal genes might be linked with intellectual disability, the majority being recessive.

anonymous asked:

i told my boss my top surgery dates but said that its for cancer prevention because i have the BRCA gene mutation. WHICH IS TRUE, BUT now i feel really bad i didnt tell her the main reason (trans) and i think this was a bad decision. im getting symptathy i feel i dont deserve, but i also really dont want to die from cancer like almost half my family. i will have to come out as stealthtrans eventually but i really fucked up btween now & then. any tips to not sound like a schemer when i do

Well, when you do come out as trans you could definitely say you used the other reason because you didn’t feel comfortable telling anyone yet (or what your reason was if otherwise). And you didn’t lie so it’s okay to get sympathy even though it’s not your main reason. You should tell said person that it makes you uneasy so they’ll stop mentioning it or at least back off a little.

- Chris

listen.  i have always wanted to be an active person. always. i could not put a number to how many times i’ve imagined myself as a runner in a parallel universe where the gene mutation that caused my disease never happened.  as a chronically ill and hella disabled person, i simply do not get to make “fitness” a part of my life, really at all.  but i do take pretty damn good care of my body.  in fact, i’d say i take more steps overall than some people who are into fitness but are already blessed with good health, like, you know, constantly going to the doctor, taking 9 prescription medicines every day, staying on top of my bloodwork, resting when i know my body needs it, which is often, having surgeries, and a plethora of other things that naturally “healthy” people don’t even have to think about.  on top of that,  i am a vegan, and i am active in minimal ways when my body allows me to be– like i love to swim and do it as much as possible.  but i will never be a “fit” girl in the sense of having a 6-pack, toned arms, and rock hard thighs.  
today, i went to therapy for the first time in a while, and i got emotional about what’s been going on with my disease and just all of the ways that it affects me.  but i came home feeling a little refreshed and took this picture. because I am strong.  My upper body strength is actually incredible from using full-time walking aids.  and aside from that, i am strong in such a deeper sense. my life is fucking difficult, and yes, all our lives are, but mine is in a constant state of overcoming what the average twenty-somethings person would consider life-shattering.  i am so fucking strong, my body is perfect even though it will never be bulging with muscles, or even all that toned, really, and i get to wear sports bras because they’re 50 times more comfortable than regular bras, damn it! so here you go, tumblr.  you are welcome. 

peep that colostomy reversal scar and that tumor bulge in my tummy.  it’s all a part of what makes me fine as fuck.  

Mutations linked to autism

Research by scientists from the Centre for Brain Research at the University of Auckland has uncovered new information about the mechanisms underlying autism spectrum disorders (ASDs), to be published in the next issue of the prestigious Journal of Neuroscience.

Principal investigator, Dr Johanna Montgomery, says the findings are highly significant: “We’re moving beyond simply what happens in ASDs and starting to understand how it happens.”

The behavioural manifestations of ASDs are well documented and include impaired communication and socialisation, learning difficulties, and repetitive or stereotyped behaviours. These behavioural characteristics are in turn associated with a wide range of gene mutations. Many of these mutated genes are responsible for the production of specific proteins in the neurons of the brain.

Dr Montgomery and her team took a close look at parts of these neurons – the synapses, which are the structures that enable brain cells to communicate with each other. This cell to cell communication is vital for a healthy brain, and underlies how we learn, remember, move and sense.

In a complex cascade of chemical and electrical signalling, information is transmitted from one neuron to another at the synapses. This process is mediated by several families of protein, some of which form the bedrock of the synapse on the ‘listening’ side. Dr Montgomery’s team chose to investigate one of these proteins, known as Shank3, because it has been identified as vital to the communication process between two neurons, and because it is known to be mutated in ASDs.

So, @amethystsworld tagged me and after much thinking, I decided to do it. So thank you hun. 

one: spell your name with song titles

A - Applause - Lady Gaga

U - Unsere Rettung - Oomph 

R - Relax, Enjoy Yourself - Randy Newman

O - Odalisque - The Decemberists

R - Red and Black - Les Miserables

E - Everything is Awesome - Lego Movie

two: Why did you choose your URL?

Because Sweety is how my BFF calls me and because I’m a Mutant. A mutated gene woke up inside me years ago and now I’ve got superpowers like “cynicism” and “super quick anger” and “perfectionism”, and even Professor X is baffled.

three: what is your middle name?

I have no official middle name nor third name because French Law sucks. (Looks who’s getting tired of this freaking country: me!) But my middle names are Hadrien and Joyce. Don’t you dare question it darlings.

four: if you could be any mythical creature, what would you be?

I think I’ll stay human for now. We humans are the best creatures ever. We are greedy, mortal, hell bound. We don not fly, do not suck blood nor breath underwater. Without otherworldly beauty and powers… What’s not to love?

Okay I know I’m not answering the question. Then, if I really have to choose, I’d say a Dahu, because seriously guys. I want to spend my life walking the same circle around a mountain.

five: favorite color?

Grey. It’s the perfect color. 

six: song you like right now?

July, July! - The Decemberists

seven: top four fandoms?

The Great Escape (until the ends of time), Black Sails (so good it hurts), The Man From UNCLE ( BOTH versions) and Les Misérables (best fandom community ever). 

tag ten people: @bittodeath, @velvetbaguette, @dounice, @cloudedstudy, @nostarondil-tiliwe, @zeldabard, @erlenwald, @framboizette someone I don’t want to bother because I love them too much but I’m dying inside to ask them, plus any of you who want to do it!