gene-mutations

EMERY'S (ELIZABETH'S) ILLNESS FACT SHEET 💾

For any of my new followers or even old friends wondering what the heck is going wrong with me medically, here’s a giant post to fill you in!

My family has problems with genetic coding, the kind that happens during cell reproduction. We have lots of spina bifida, MS and other chronic illnesses related to gene mutations in our family.

I have a one of a kind (as far as I know) genetic mutation that I like to call …
🎉Emery’s 15 year hell, 2.0: progressive update🎉

My mutation affects my lungs ability to regulate growth rates. More simply, my lungs don’t know how, when, where or how much to grow or not grow. They grow an abundance of excess tissue in random spurts, attaching to (and thus attacking) my other organs and muscles, and grabbing on to other parts of my lungs, creating pockets and more recently closing of parts of my lungs all together.

🎀Current Chronic symptoms are: chronic pain, muscle weakness in lower extremities, severely decreased lung function/volume (about left 68% according to recent tests)
🎀leading to: oxygen deprivation and then organ damage and eventually failure due to lack of properly oxygenated blood, occasional inability to move properly, and frequent hospital and clinic visits 😷

Because of the illnesses daily effect on my life, I consider myself a part of the spoonie community. 🐎🐄 I love you all so much, thanks for all the support, even for an invisible illness homie like me 😘

All the medication AND vitamins I’m on (for this and all my other stuff):
Thorne research neurochondia
Vitamin C ***
Cinnamon extract
Magnesium Taurate
Sam-E
Double Strength Zinc Picolinate
Alpha-Lipoic Acid
Vitamin D ***
5-MTHF (anti-mutation)
Polyflora type AB
Chromium Complex ***
Cod Liver Oil
Glutathione
Dipan-9
Aspirin
Drenamin
Paraplex
Cataplex A-C-P
Ambrotose
Lithium + Latuda + Ariprazole + Zoloft

I was diagnosed at age 10, after my choir director realized I couldn’t get as much air as the other kids. For more than a year, I was a medical mystery until a doctor took a look at my genomics scan and then made the rash decision to open me up and look inside. I love you Dr. Larson ❤️

SO HERE ARE THE FACTS:
At age 10, I was given 15 years to live.
At age 15, I have 10 productive years left.

In those 10 years, I am not only living with the symptoms of this illness but other chronic illnesses as well: I also have endometriosis (like my lung condition but for reproductive organs), scoliosis and organ displacement, OCD, PTSD, bipolar disorder, and a BPD.

Even so, I have things I want to accomplish, a master bucket list if you will.☺️😚😊😘
Visit: Italy, New York, Prague, (TYC 2k14 y 17)
Go to VidCon
Go to a Ted Talks conference
Get 1000 subscribers on YouTube
Go to a pride parade
Go on a date
Get my degree
(current plan: anthropology (specializing in gender and sexuality studies and minor in psychology)
Go to an apple event
See a concert in Madison Square Garden
Fly 1st class with the bed seats
Stay in the Tacoma Dome hotel special suite
March on Mayday

👯 I AM MORE THAN MY ILLNESS AND MY PROGNOSIS 😺

I am a daughter at times, a sister, a friend, a lover, a substitute mom, a musician, a singer (a singer with a lung condition, wow, but a damn good one) and most of all, I’m a human being with hopes and dreams and feelings.
I love deeply, I live with the time I’m given and want every moment to be as beautiful as can be.

I’ll be doing these every 2 weeks or so :) maybe by the end of the week, I’ll answer some of your questions if you want, like an FAQ. Send me an ask (anon or not) or fan mail or even contact me through the stuff in my bio. 😀 OR come find me if you know me in real life, I’ll answer all of your questions, promise. Just be nice 😇

Lots of Love, ❤️

Mutants in the MCU.

I totally just came up with a perfect way to eventually explain mutants in the MCU when the rights eventually come back home, without in the process cutting Wanda and Pietro out.  

So let’s consider mutation and genetics.  

Imagine if you will an interpretation of mutants where the mutant gene is recessive and not dominant.  Mutation is, in nature, random.  Often it stays with the individual but if the mutation is useful it continues on in the gene pool.  You have cases where the mutation is in action, like Magneto or Wolverine, who are the source point.  Their genes mutated in development.  If they have children with other mutants, the mutation is dominant and presents itself in their children.  If they have children with non-mutants, the gene does not manifest.

UNLESS, such as in the case of Pietro and Wanda Maximoff whose mother was not a mutant, their genetics are experimented on.  Science triggers the mutant gene as an external force.  So Wanda and Pietro are viewed by Hydra scientists are exceptional test subjects who responded positively to the experimentation, without their knowing that the gene was already there ready for it to be pushed. 

It’s not like in the comics (contrary to sort of popular belief in how we see the marvel universe) mutants are SUPER common.  It’s not like one in every 10 people is a mutant.  It’s more like one in every 100,000 anyway, at the very least.  Especially given the genetic aspect of it, mutation community forms in population bubbles.  Like New York.  New York is a mutant population bubble.  Not that they won’t show up and don’t show up everywhere, there is just less probability given population percentages.  

GENETICS.

3

Top Real-Life Super Powers

Genetic mutations and advanced technology can give comic book characters super-human abilities. And the same holds true in real life.

Sure, humans don’t yet have the ability to shape-shift or walk through walls or, as is the case with Wolverine, heal in seconds from just about any injury.

But there are a few other super powers that are within practical reach (and no shortage of people claiming to possess super powers).

Explore some examples of super human powers and abilities in the real world…

flame on…

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.

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 

Neuroscientists identify key role of language gene

Neuroscientists have found that a gene mutation that arose more than half a million years ago may be key to humans’ unique ability to produce and understand speech.

Researchers from MIT and several European universities have shown that the human version of a gene called Foxp2 makes it easier to transform new experiences into routine procedures. When they engineered mice to express humanized Foxp2, the mice learned to run a maze much more quickly than normal mice.

The findings suggest that Foxp2 may help humans with a key component of learning language — transforming experiences, such as hearing the word “glass” when we are shown a glass of water, into a nearly automatic association of that word with objects that look and function like glasses, says Ann Graybiel, an MIT Institute Professor, member of MIT’s McGovern Institute for Brain Research, and a senior author of the study.

“This really is an important brick in the wall saying that the form of the gene that allowed us to speak may have something to do with a special kind of learning, which takes us from having to make conscious associations in order to act to a nearly automatic-pilot way of acting based on the cues around us,” Graybiel says.

Wolfgang Enard, a professor of anthropology and human genetics at Ludwig-Maximilians University in Germany, is also a senior author of the study, which appears in the Proceedings of the National Academy of Sciences this week. The paper’s lead authors are Christiane Schreiweis, a former visiting graduate student at MIT, and Ulrich Bornschein of the Max Planck Institute for Evolutionary Anthropology in Germany.

All animal species communicate with each other, but humans have a unique ability to generate and comprehend language. Foxp2 is one of several genes that scientists believe may have contributed to the development of these linguistic skills. The gene was first identified in a group of family members who had severe difficulties in speaking and understanding speech, and who were found to carry a mutated version of the Foxp2 gene.

In 2009, Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology, and his team engineered mice to express the human form of the Foxp2 gene, which encodes a protein that differs from the mouse version by only two amino acids. His team found that these mice had longer dendrites — the slender extensions that neurons use to communicate with each other — in the striatum, a part of the brain implicated in habit formation. They were also better at forming new synapses, or connections between neurons.

Pääbo, who is also an author of the new PNAS paper, and Enard enlisted Graybiel, an expert in the striatum, to help study the behavioral effects of replacing Foxp2. They found that the mice with humanized Foxp2 were better at learning to run a T-shaped maze, in which the mice must decide whether to turn left or right at a T-shaped junction, based on the texture of the maze floor, to earn a food reward.

The first phase of this type of learning requires using declarative memory, or memory for events and places. Over time, these memory cues become embedded as habits and are encoded through procedural memory — the type of memory necessary for routine tasks, such as driving to work every day or hitting a tennis forehand after thousands of practice strokes.

Using another type of maze called a cross-maze, Schreiweis and her MIT colleagues were able to test the mice’s ability in each of type of memory alone, as well as the interaction of the two types. They found that the mice with humanized Foxp2 performed the same as normal mice when just one type of memory was needed, but their performance was superior when the learning task required them to convert declarative memories into habitual routines. The key finding was therefore that the humanized Foxp2 gene makes it easier to turn mindful actions into behavioral routines.

The protein produced by Foxp2 is a transcription factor, meaning that it turns other genes on and off. In this study, the researchers found that Foxp2 appears to turn on genes involved in the regulation of synaptic connections between neurons. They also found enhanced dopamine activity in a part of the striatum that is involved in forming procedures. In addition, the neurons of some striatal regions could be turned off for longer periods in response to prolonged activation — a phenomenon known as long-term depression, which is necessary for learning new tasks and forming memories.

Together, these changes help to “tune” the brain differently to adapt it to speech and language acquisition, the researchers believe. They are now further investigating how Foxp2 may interact with other genes to produce its effects on learning and language.

This study “provides new ways to think about the evolution of Foxp2 function in the brain,” says Genevieve Konopka, an assistant professor of neuroscience at the University of Texas Southwestern Medical Center who was not involved in the research. “It suggests that human Foxp2 facilitates learning that has been conducive for the emergence of speech and language in humans. The observed differences in dopamine levels and long-term depression in a region-specific manner are also striking and begin to provide mechanistic details of how the molecular evolution of one gene might lead to alterations in behavior.”

genetically modified foods still lack labels saying they are “GMOs”

would you eat genetically modified food if you knew what it was?

Genetically Modified Corn-Cancer Link Based on Poor Science

A paper was published indicating that Monsanto’s genetically modified corn could be linked to tumors.

When other scientists looked at the research they cried, “fantasy statistics” and “fishing” for answers

it’s poppin’…

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.

A_Primer_on_DNA_and_DNA_Replication

Larry H. Bernstein, MD, FCAP, Reporter and Curator

Leaders in Pharmaceutical Intelligence

http://pharmaceuticalintelligence.com/2014-28-07/A_Primer_on_DNA_and_DNA_Replication

A Primer on DNA and DNA Replication

DNA Replication

DNA carries the information for making all of the cell’s proteins. These pro­teins implement all of the functions of a living organism and determine the…

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(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.

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.”

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.”