Scientists Have Pinpointed the Gene Responsible for Down Syndrome


IN BRIEF

A team of researchers from Singapore and the United Kingdom have discovered an enzyme that regulates sperm and egg cell production, which may be linked to Down Syndrome, Patau Syndrome, and other chromosomal aberrations.

UNDERSTANDING THE LINK

Humans have 23 pairs of chromosomes in every cell in their bodies, except for their reproductive cells or gamete cells (sperm or egg), which contain 23 chromosomes. The reason why chromosomes come in pairs is that one pair comes from the egg, and the other from the sperm. So when gametes fuse with each other, they end up as a single cell having two copies of each chromosome.

Gamete cells are produced by a process called meiosis — a type of cell division with two rounds of nuclear division, to make sure that the number of chromosomes in the parent cell is halved. Sometimes, though, errors occur during cell division, which may result to offsprings having abnormal number of chromosomes — a phenomenon called aneuploidy.

Aneuploidy causes Down Syndrome — the most common genetic condition, Patau Syndrome, and other genetic disorders. It is also the leading cause of miscarriage.

Image Credit: iStock/koya79

PLAYING A PIVOTAL ROLE

The research team, led by Dr. Prakash Arumugam from the National University of Singapore, noted how the process of meiosis can affect chromosomal irregularities: “Understanding how meiosis is regulated is of great importance to understanding the causes of aneuploidy and genetic disorders in human,” said Dr Gary Kerr and the team, writing in the journal Scientific Reports.

The researchers have discovered a particular enzyme which plays an essential role in chromosome segregation in meiosis. They identified this enzyme as PP2ACdc55, which is involved in various cellular processes. It was also shown from the research team’s previous findings that PP2ACdc55 plays a vital role in controlling the timing of meiosis, thus preventing the cells from prematurely exiting phases of cell division.

The scientists tracked the enzyme on yeast models using fluorescent tagging, and analyzed the resulting mutant yeast strains, characterized the mutations and determined the role of the Cdc55 gene. Their results suggest that the gene might have a role in meiotic chromosome segregation. This is, without a doubt, a step forward, but we still don’t know what causes the process to go wrong.

Scientists identify brain molecule that triggers schizophrenia-like behaviors, brain changes


Scientists at The Scripps Research Institute (TSRI) have identified a molecule in the brain that triggers schizophrenia-like behaviors, brain changes and global gene expression in an animal model. The research gives scientists new tools for someday preventing or treating psychiatric disorders such as schizophrenia, bipolar disorder and autism.

“This new model speaks to how schizophrenia could arise before birth and identifies possible novel drug targets,” said Jerold Chun, a professor and member of the Dorris Neuroscience Center at TSRI who was senior author of the new study.

The findings were published April 7, 2014, in the journal Translational Psychiatry.

What Causes Schizophrenia?

According to the World Health Organization, more than 21 million people worldwide suffer from schizophrenia, a severe psychiatric disorder that can cause delusions and hallucinations and lead to increased risk of suicide.

Although psychiatric disorders have a genetic component, it is known that environmental factors also contribute to disease risk. There is an especially strong link between psychiatric disorders and complications during gestation or birth, such as prenatal bleeding, low oxygen or malnutrition of the mother during pregnancy.

In the new study, the researchers studied one particular known risk factor: bleeding in the brain, called fetal cerebral hemorrhage, which can occur in utero and in premature babies and can be detected via ultrasound.

In particular, the researchers wanted to examine the role of a lipid called lysophosphatidic acid (LPA), which is produced during hemorrhaging. Previous studies had linked increased LPA signaling to alterations in architecture of the fetal brain and the initiation of hydrocephalus (an accumulation of brain fluid that distorts the brain). Both types of events can also increase the risk of psychiatric disorders.

“LPA may be the common factor,” said Beth Thomas, an associate professor at TSRI and co-author of the new study.

Mouse Models Show Symptoms

To test this theory, the research team designed an experiment to see if increased LPA signaling led to schizophrenia-like symptoms in animal models.

Hope Mirendil, an alumna of the TSRI graduate program and first author of the new study, spearheaded the effort to develop the first-ever animal model of fetal cerebral hemorrhage. In a clever experimental paradigm, fetal mice received an injection of a non-reactive saline solution, blood serum (which naturally contains LPA in addition to other molecules) or pure LPA.

The real litmus test to show if these symptoms were specific to psychiatric disorders, according to Mirendil, was “prepulse inhibition test,” which measures the “startle” response to loud noises. Most mice—and humans—startle when they hear a loud noise. However, if a softer noise (known as a prepulse) is played before the loud tone, mice and humans are “primed” and startle less at the second, louder noise. Yet mice and humans with symptoms of schizophrenia startle just as much at loud noises even with a prepulse, perhaps because they lack the ability to filter sensory information.

Indeed, the female mice injected with serum or LPA alone startled regardless of whether a prepulse was placed before the loud tone.

Next, the researchers analyzed brain changes, revealing schizophrenia-like changes in neurotransmitter-expressing cells. Global gene expression studies found that the LPA-treated mice shared many similar molecular markers as those found in humans with schizophrenia. To further test the role of LPA, the researchers used a molecule to block only LPA signaling in the brain.

This treatment prevented schizophrenia-like symptoms.

Implications for Human Health

This research provides new insights, but also new questions, into the developmental origins of psychiatric disorders.

For example, the researchers only saw symptoms in female mice. Could schizophrenia be triggered by different factors in men and women as well?

“Hopefully this animal model can be further explored to tease out potential differences in the pathological triggers that lead to disease symptoms in males versus females,” said Thomas.

In addition to Chun, Thomas and Mirendil, authors of the study, “LPA signaling initiates schizophrenia-like brain and behavioral changes in a mouse model of prenatal brain hemorrhage,” were Candy De Loera of TSRI; and Kinya Okada and Yuji Inomata of the Mitsubishi Tanabe Pharma Corporation.

Smoking Injurious to Genes Too


Here comes another shocker for those reluctant to kick the butt.

Smoking not only affects your health but also increases health risks of your children and grandchildren; today’s puffs of pleasure can permanently damage your genes, according to a new study.

Smoking can also affect the genes important for sperm quality or immune response.

The research findings from Uppsala University and Uppsala Clinical Research Center of Sweden showed that smoking alters several genes that can be associated with health problems for smokers, such as increased risk for cancer and diabetes.

The research, led by Asa Johansson, researcher at the Department of Immunology, Genetics and Pathology, said the genes of smokers as well tobacco users can change and expose them to more health risks.

However, according to the findings, tobacco itself may not be the cause of gene alterations, but the different elements that are formed when the tobacco is burnt.

“Our results therefore indicate that the increased disease risk associated with smoking is partly caused by epigenetic changes. A better understanding of the molecular mechanism behind diseases and reduced body function might lead to improved drugs and therapies in the future,” Johansson said.

The findings of the study have been published in the journal Human Molecular Genetics.

Designer Sperm Passes Selected Genes to Future Generations.


  • Frustrated by slow progress in gene therapy, a team of scientists opted for an unconventional approach. Instead of relying on the oocyte as a substrate for genetic modification, they took a closer look at male germ cells, including mature sperm. Sperm, owing to their accessibility, seemed to offer a convenient route to transgenesis.

    The scientists, based at the Royal Veterinary College in North Mimms, United Kingdom, used a viral vector to insert genetic material into mouse spermatozoa. Then the spermatozoa were used in an in vitro fertilization procedure. In the resulting embryos, the genetic material was found to be present and active—and inheritable. The genetic material that had been introduced to the spermatozoa was, the scientists confirmed, still functional after passing through at least three generations of mice.

    The scientists presented their results December 2 in The FASEB Journal, in an article entitled “Efficient generation of transgenic mice by lentivirus-mediated modification of spermatozoa.” In this article, the authors wrote, “When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were incubated with mouse spermatozoa, these sperm were highly successful in producing transgenics.” Then, after embryo transfer, “≥42% of founders were found to be transgenic for GFP.”

    The authors also noted that they used inverse PCR for integration site analysis, which allowed them to show that at least one or two copies of GFP had been integrated in the transgenic animals, mapping to different chromosomes. GFP expression was detected in a wide range of murine tissues, including testis.

    This transgenic technology—if successful in humans—could lead to a new frontier in genetic medicine in which diseases and disorders are effectively cured, and new human attributes, such as organ regeneration, may be possible.

    “Transgenic technology is a most important tool for researching all kinds of disease in humans and animals, and for understanding crucial problems in biology,” said Anil Chandrashekran, Ph.D., a study author and research associate at the Royal Veterinary College.

    In detailing the more immediate applications of their work, the authors wrote, “This relatively simple, yet highly efficient, technique for generating transgenic animals by transducing spermatozoa with lentiviral vectors in vitro is a powerful tool for the study of fertilization/preimplantation development, vertical viral gene transmission, gene function and regulation, and epigenetic inheritance.

    Offering a more expansive view of the authors’ work, Gerald Weissmann, M.D., editor-in-chief of The FASEB Journal, noted that using modified sperm to insert genetic material has the potential to be a major breakthrough not only in future research, but also in human medicine.

    “It facilitates the development of transgenic animal models, and may lead to therapeutic benefits for people as well,” said Dr. Weissman. “For years we have chased effective gene therapies and have hit numerous speed bumps and dead ends. If we are able to able to alter sperm to improve the health of future generations, it would completely change our notions of ‘preventative medicine.'”

 

Gene responsible for hereditary cancer syndrome found to disrupt critical growth-regulating pathway.


 Whitehead Institute scientists report that the gene mutated in the rare hereditary disorder known as Birt-Hogg-Dubé cancer syndrome also prevents activation of mTORC1, a critical nutrient-sensing and growth-regulating cellular pathway.

This is an unexpected finding, as some cancers keep this pathway turned on to fuel their unchecked growth and expansion. In the case of Birt-Hogg-Dubé syndrome, the mutated gene prevents mTORC1 pathway activation early in the formation of tumors. Reconciling these opposing roles may give scientists a new perspective on how cancer cells can distort normal cellular functions to maintain their own harmful ways.

Cells use the mTORC1 (for “mechanistic target of rapamycin complex 1”) pathway to regulate growth in response to the availability of certain nutrients, including amino acids. Whitehead Member David Sabatini and other researchers have teased apart many components of this pathway, but the precise mechanism by which nutrient levels are actually sensed has remained elusive. Recently, Sabatini and his lab determined that a family of proteins known as Rag GTPases act as a switch for the pathway—when nutrients are present, the Rag proteins turn on the mTORC1 pathway.

Now, several members of the Sabatini lab, including graduate student Zhi-Yang Tsun, have determined that the FLCN protein acts as a trigger to activate the Rag protein switch. Their work is described in the November 7 issue of the journal Molecular Cell.

“Zhi has ascribed a molecular function to this protein, and that’s a major contribution,” says Sabatini, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. “For the first time, we have a biochemical function that’s associated with it. And in my view, that’s an important first step to understanding how it might be involved in cancer.”

Before Tsun’s work, very little was known about FLCN’s role in the cell. In the early 2000s, scientists determined that mutations in the gene coding for FLCN caused the rare cancer Birt-Hogg-Dubé syndrome, but the syndrome’s symptoms offered little insight into FLCN’s molecular function.

Birt-Hogg-Dubé syndrome causes unsightly but benign hair follicle tumors on the face, benign tumors in the lungs that can lead to collapsed lungs, and kidney cancer. The syndrome is an autosomal dominant disorder, which means that a child inheriting one mutated copy of the FLCN gene will eventually develop the syndrome. Currently, the disease is managed by treating symptoms, but no cure exists.

FLCN’s dual roles—as a cause of a rare cancer in its mutated form and as a trigger for a growth pathway that is often hijacked in cancer cells—has prompted Tsun and Sabatini to rethink how a mutation can push cells to become cancerous.

“Basically, the mTORC1 pathway is essential for life,” explains Tsun. “So when you lose this nutrient switch or if it can’t be turned on, then the cell seems to freak out and cause all other growth promoting pathways to be turned on to somehow overcompensate for this loss. And this is actually what we see in patient tumors.”

For Birt-Hogg-Dubé syndrome patients and their families, better understanding of FCLN’s function moves the field one step closer to developing a therapy.

“Usually diseases are first described, then the responsible gene or genes are identified, and then that gene’s molecular function is figured out,” says Tsun. “And you need to know the gene’s function before you can start working on drugs or therapy. We’ve done that third step, which is a very important discovery for these patients.”

Why a Lucky Few Can Eat to Their Heart’s Content.


We all know people who seem to have been born with good genes—they may smoke, never exercise, or consume large amounts of bacon, yet they remain seemingly healthy. Now, researchers have found that individuals who carry a rare genetic mutation that controls the blood levels of certain fats, or lipids, are protected from heart disease. The result, reported here yesterday at the annual meeting of the American Society of Human Genetics, suggests that a drug mimicking this effect could prevent heart disease, a major killer.

Triglycerides are lipids that the body makes from unused calories in food and later burns as fuel. Doctors often monitor patients’ blood levels of these compounds because higher levels have been linked to a greater risk of heart disease.

One player in processing triglycerides is a protein called ApoC-III that is encoded by the gene APOC3. Five years ago, researchers discovered a mutation in APOC3 in 5% of the Amish population in Lancaster County, Pennsylvania. Those with this variant had unusually low levels of triglycerides after consuming a fat-laden milkshake. They also had only half as much ApoC-III protein in their blood, and they were less likely to develop calcification of coronary arteries, which can lead to coronary heart disease.

The Amish group was too small to allow researchers to directly link the genetic mutation to less heart disease, however. And it wasn’t clear whether the gene would show up in non-Amish people.

Now, researchers have found APOC3 mutations in the general U.S. population. They sequenced the protein-coding DNA, or exomes, of 3734 white and African-American volunteers, then combed through the data for genetic variants linked to triglyceride levels. A few people turned out to have either the Amish APOC3 mutation or one of three other variants in APOC3 that also disable this copy of the gene. When the team checked the DNA of a larger group of nearly 111,000 people, they found that about one in 200 carried one of the four APOC3 variants, reported Jacy Crosby of the University of Texas Health Science Center, Houston, who represented a large consortium called the National Heart, Lung, and Blood Institute Exome Sequencing Project.

The 500 or so people with one of these APOC3 variants not only had less ApoC-III in their blood and 38% lower triglyceride levels than the average person; they also had a 40% lower risk of coronary heart disease, whose effects include heart attacks. This result firms up the link between APOC3 and heart disease and also supports a possible prevention strategy, Crosby said: Reducing levels of the ApoC-III protein could potentially lower lipid levels and protect against heart disease. One such drug is already in clinical testing, she noted.

The new study “is exciting, but one has to be cautious” about whether such a drug will work, says geneticist Stephen Rich of the University of Virginia in Charlottesville. That’s because inhibiting ApoC-III late in life may not mimic being born with an APOC3 mutation, which protects for a lifetime, he says.

Faces are sculpted by ‘junk DNA’


Scientists have identified thousands of regions in the genome that control the activity of genes for facial features.

Smiling child

‘Transcriptional enhancers‘ switch genes on or off in different parts of the face. Photograph: Rex Features

Researchers have started to figure out how DNA fine-tunes faces. In experiments on mice, they have identified thousands of regions in the genome that act like dimmer switches for the many genes that code for facial features, such as the shape of the skull or size of the nose.

Specific mutations in genes are already known to cause conditions such as cleft lips or palates. But in the latest study, a team of researchers led by Axel Visel of the Lawrence Berkeley National Laboratory in Berkeley, California, wanted to find out how variations seen across the normal range of faces are controlled.

Though everybody’s face is unique, the actual differences are relatively subtle. What distinguishes us is the exact size and position of things like the nose, forehead or lips. Scientists know that our DNA contains instructions on how to build our faces, but until now they have not known exactly how it accomplishes this.

Visel’s team was particularly interested in the portion of the genome that does not encode for proteins – until recently nicknamed “junk” DNA – but which comprises around 98% of our genomes. In experiments using embryonic tissue from mice, where the structures that make up the face are in active development, Visel’s team identified more than 4,300 regions of the genome that regulate the behaviour of the specific genes that code for facial features.

The results of the analysis are published on Thursday in Science.

These “transcriptional enhancers” tweak the function of hundreds of genes involved in building a face. Some of them switch genes on or off in different parts of the face, others work together to create, for example, the different proportions of a skull, the length of the nose or how much bone there is around the eyes.

“If you think about face development, a gene that is important for both development of the nose and the mouth might have two different enhancers and one of them activates the gene in the nose and the other just in the mouth,” said Visel.

“Certainly, one evolutionary advantage that is associated with this is that you can now change the sequence of the nose or mouth enhancers and, independently, affect the activity of the gene in just one structure or the other. It may be a way a way that nature has evolved in which you can fine-tune the expression of genes in complex ways without having to mess with the gene itself. If you destroy the protein itself that usually has much more severe consequences.”

In further experiments to test their findings, the scientists genetically engineered mice to lack three of the enhancers they had identified. They then used CT (computed tomography) scanning to build 3D images of the resulting mouse skulls at the age of eight weeks.

Compared with normal mice, the skulls of the modified mice had microscopic, but consistent, changes in the length and width of the faces, as expected. Importantly, all of the modified mice only showed subtle changes in their faces, and there were no serious harmful results such as cleft lips or palates.

Though the work was done in mice, Visel said that the lessons transfer across to humans very well. “When you look at the anatomy and development of the mouse versus the human, we find that the faces are actually very similar. Both are mammals and they have, essentially, all the same major bones and structures in their skulls, they just have a somewhat different shape in the mouse. The same genes that are important for mouse face development are important in humans.”

Visel said that the primary use of this information, beyond basic genetic knowledge, would be as part of a diagnostic tool, for clinicians who might be able to advise parents if they are likely to pass on particular mutations to their children.

Peter Hammond, a professor of computational biology at University College London‘s Institute of Child Health, who researches genetic effects on facial development, said understanding how faces develop can be important for health.

“There are many genetic conditions where the face is a first clue to diagnosis, and even though the facial differences are not necessarily severe the condition may involve significant intellectual impairment or adverse behavioural traits, as well as many other effects,” he said. “Diagnosis is important for parents as it reduces the stress of not knowing what is wrong, but also can be important for prognosis.”

The technology to go beyond diagnosis and make precise corrections of the genome does not yet exist and, even if it did, it is not clear that changing genes or enhancers to create “designer” faces would be worthwhile. “I don’t think it would be desirable to even attempt that. It’s certainly not something that motivates me to work on this,” said Visel. “And I don’t think anyone working in this field would seriously view this as a possible motivation.”

Metabolism ‘obesity excuse’ true


Obese child

The mocked “obesity excuse” of being born with a slow metabolism is actually true for some people, say researchers.

A team at the University of Cambridge has found the first proof that mutated DNA does indeed slow metabolism.

The researchers say fewer than one in 100 people are affected and are often severely obese by early childhood.

The findings, published in the journal Cell, may lead to new obesity treatments even for people without the mutation.

Scientists at the Institute of Metabolic Science, in Cambridge, knew that mice born without a section of DNA, a gene called KSR2, gained weight more easily.

It slows the ability to burn calories and that’s important as it’s a new explanation for obesity”

Prof Sadaf Farooqi University of Cambridge

But they did not know what affect it may be having in people, so they analysed the DNA of 2,101 severely obese patients.

Some had mutated versions of KSR2.

It had a twin effect of increasing their appetite while their slowing metabolism.

“You would be hungry and wanting to eat a lot, you would not want to move because of a slower metabolism and would probably also develop type 2 diabetes at a young age,” lead researcher Prof Sadaf Farooqi told the BBC.

She added: “It slows the ability to burn calories and that’s important as it’s a new explanation for obesity.”

Munching on chips
The mutation delivers a double-whammy by increasing the drive to eat and reducing calorie burn

KSR2 is mostly active in the brain and it affects the way individual cells interpret signals, such as the hormone insulin, from the blood. This in turn affects the body’s ability to burn calories.

Prof Farooqi said the metabolism argument had been derided by doctors, as well as wider society, due to a lack of evidence that metabolism was slowed in obese patients. In many cases obese patients have an elevated metabolism to cope with fuelling a much larger body.

She said less than 1% of people had mutated versions of the gene and some would be a normal weight, but about 2% of children who were obese by the age of five would have the mutated gene.

However, if drugs could be developed to target problems with KSR2, then it might be beneficial to anyone who is too fat.

“Other genetic disorders, such as in blood pressure, have shown that even where there’s a normal gene, targeting the pathway can still help,” Prof Farooqi said.

The amount and types of food eaten, as well as levels of exercise, directly affect weight, but some people at more risk of becoming obese that others.

Obesity can run in families. The other obesity genes that have been discovered tend to affect appetite.

People have two copies of the FTO gene – one from each parent – and each copy comes in a high- and a low-risk form. Those with two-high risk copies of the FTO gene are thought to be 70% more likely to become obese than those with low-risk genes.

It makes fatty foods more tempting and alters levels of the hunger hormone ghrelin.

Dr Katarina Kos, from the University of Exeter Medical School, said: “It is an exciting and interesting breakthrough, this is a new pathway predisposing people to obesity.

“But it does exist in obese and lean people so you still need the obesogenic environment.”

The New Deadliest Substance Known to Man Is Top Secret (For Now)


Scientists recently discovered a new type of botulinum toxin (a.k.a. botox) that they believe is the deadliest substance known to man. Because they’ve yet to discover an antitoxin, researchers won’t publish the details of gene sequence due to security concerns—a first for the scientific community. Thank God.

When scientists say this stuff is deadly, they mean it. It takes an injection of just 2 billionths of a gram or inhaling 13 billionths of a gram to kill an adult. A spoonful of the stuff in a city’s water supply could be catastrophic. The toxin, which comes from the bacterium Clostridium botulinum, blocks the chemical that makes nerves work, causing botulism and death by paralysis. In a comment accompanying a newly published journal article on the new botox, Stanford Medical School professor David Relman said the substance posed “an immediate and unusually serious risk to society.”

You’d be right to wonder: If this stuff is so dangerous, why do we have it in the first place? Well, it’s not manmade if that’s what you’re thinking. Before this new discovery, there were seven known branches on the botulinum family tree, but researchers recently found an eighth type of toxin in stool samples of an infant with botulism. It just so turns out that eighth type, known as type H, is the deadliest substance in the world. Scientists are withholding the genetic sequence so that terrorists, for instance, can’t synthesize it and do something terrible. Terrorists do like botox, too. It was one of these toxins that the Japanese cult Aum Shinrikyo tried to release in downtown Tokyo in the 1990s.

Despite the somewhat sensational nature of this latest discovery, everything is okay for now. This is, however, a rude reminder of how scientific discoveries can always be twisted into weapons of warfare. Unless we keep them secret, that is.

Researchers identify key proteins that help establish cell function


Researchers at the University of California, San Diego School of Medicine have developed a new way to parse and understand how special proteins called “master regulators” read the genome, and consequently turn genes on and off.

Writing in the October 13, 2013 Advance Online Publication of Nature, the scientists say their approach could make it quicker and easier to identify specific gene associated with increased – an essential step toward developing future targeted treatments, preventions and cures for conditions ranging from diabetes to neurodegenerative disease.

“Given the emerging ability to sequence the genomes of individual patients, a major goal is to be able to interpret that DNA sequence with respect to disease risk. What diseases is a person genetically predisposed to?” said principal investigator Christopher Glass, MD, PhD, a professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego.

“Mutations that occur in protein-coding regions of the genome are relatively straight forward, but most mutations associated with disease risk actually occur in regions of the genome that do not code for proteins,” said Glass. “A central challenge has been developing a strategy that assesses the potential functional impact of these non-coding mutations. This paper lays the foundation for doing so by examining how natural genetic variation alters the function of genomic regions controlling gene expression in a cell specific-manner.”

Cells use hundreds of different proteins called transcription factors to “read” the genome, employing those instructions to turn genes on and off. These factors tend to be bound close together on the genome, forming functional units called “enhancers.” Glass and colleagues hypothesized that while each cell has tens of thousands of enhancers consisting of myriad combinations of factors, most enhancers are established by just a handful of special transcription factors called “master regulators.” These master regulators play crucial, even disproportional, roles in defining each cell’s identity and function, such as whether it will be a muscle, skin or heart cell.

“Our main idea was that the binding of these master regulators is necessary for the co-binding of the other transcription factors that together enable enhancers to regulate the expression of nearby genes,” Glass said.

The scientists tested and validated their hypothesis by looking at the effects of approximately 4 million DNA sequence differences affecting master regulators in macrophage cells in two strains of mice. Macrophages are a type of immune response cell. They found that DNA sequence mutations deciphered by master regulators not only affected how they bound to the genome, but also impacted neighboring needed to make functional .

The findings have practical importance for scientists and doctors investigating the genetic underpinnings of disease, said Glass. “Without actual knowledge of where the master regulator binds, there is relatively little predictive value of the DNA sequence for non-coding variants. Our work shows that by collecting a focused set of data for the master regulators of a particular cell type, one can greatly reduce the ‘search space’ of the in a particular cell type that would be susceptible to the effects of mutations. This allows prioritization of mutations for subsequent analysis, which can lead to new discoveries and real-world benefits.”

Source:  University of California – San Diego