Posts Tagged ‘gene’

By Tereza Pultarova

About 4 percent of the people on Earth experience a mysterious phenomenon called synesthesia: They hear a sound and automatically see a color; or, they read a certain word, and a specific hue enters their mind’s eye. The condition has long puzzled scientists, but a small new study may offer some clues.

The study, published March 5 in the journal Proceedings of the National Academy of Sciences, offers insight into what might be happening in the brains of people with synesthesia.

Previous “studies of brain function using magnetic resonance imaging confirm that synesthesia is a real biological phenomenon,” said senior study author Simon Fisher, director of the Max Planck Institute for Psycholinguistics in the Netherlands. For example, when people with synesthesia “hear” color, brain scans show that there’s activity in the parts of the brain linked to both sight and sound, he said. (Not all people with the condition “hear” sights, however; the condition can also link other senses.)Indeed, the brains of people with synesthesia previously have been shown to be more connected across different regions than the brains of people whose senses are not cross-linked, Fisher told Live Science. The question, however, was what causes this different brain wiring, he said.

To answer that question, Fisher and his team looked to genetics.

Synesthesia frequently runs in families, so the researchers decided to look for genes that might be responsible for the development of the condition. They chose three families, in which multiple members across at least three generations had a specific type of synesthesia, the so-called sound-color synesthesia, meaning that hearing sounds evokes perceptions of colors. Typically, a specific sound or musical tone is consistently associated with a specific color for people who have this type of synesthesia. However, different members of a single family can see different colors when hearing the same sound, Fisher said.

The scientists used DNA sequencing to study the participants’ genes, Fisher said. Then, to identify genes that might be responsible for the condition, the scientists compared the genes of family members with synesthesia to the genes of family members without it, he said.

But the findings didn’t yield a straightforward result: “There was not a single gene that could explain synesthesia in all three families,” Fisher said. Instead, “there were 37 candidate variants,” or possible gene variations, he said.

Because the study included only a small number of people, there wasn’t enough data to single out the specific genes, of the 37 possibilities, that played a role in synesthesia. So, instead, the scientists looked at the biological functions of each gene to see how it could be related to the development of the condition. “There were just a few biological themes that were significantly enriched across the candidate genes identified,” Fisher said. “One of those was axonogenesis, a crucial process helping neurons get wired up to each other in the developing brain.” Axonogenesis refers to the development of neurons.

This is consistent with prior findings of altered connectivity in brain scans of people with synesthesia, Fisher said. In other words, the genes identified in the study play a role in how the brain is wired, offering a potential explanation for why the brains of people with synesthesia appear to be wired differently.


A group of genes and genetic switches involved in age-related brain deterioration have been identified by scientists at the Babraham Institute, Cambridge and Sapienza University, Rome. The research, published online today (5th March) in Aging Cell, found that changes to one of these genes, called Dbx2, could prematurely age brain stem cells, causing them to grow more slowly. The study was led jointly by Giuseppe Lupo and Emanuele Cacci in Italy and Peter Rugg-Gunn in the UK.

Cells in the brain are constantly dying and being replaced with new ones produced by brain stem cells. As we age, it becomes harder for these stem cells to produce new brain cells and so the brain slowly deteriorates. By comparing the genetic activity in brain cells from old and young mice, the scientists identified over 250 genes that changed their level of activity with age. Older cells turn some genes, including Dbx2, on and they turn other genes off.

By increasing the activity of Dbx2 in young brain stem cells, the team were able to make them behave more like older cells. Changes to the activity of this one gene slowed the growth of brain stem cells. These prematurely aged stem cells are not the same as old stem cells but have many key similarities. This means that many of the genes identified in this study are likely to have important roles in brain ageing.

The research also identified changes in several epigenetic marks – a type of genetic switch – in the older stem cells that might contribute to their deterioration with age. Epigenetic marks are chemical tags attached to the genome that affect the activity of certain genes. The placement of these marks in the genome change as we age and this alters how the cells behave. The researchers think that some of these changes that happen in the brain may alter causing brain stem cells to grow more slowly.

First author on the paper, Dr Giuseppe Lupo, Assistant Professor at Sapienza University said: “The genes and gene regulators that we identified are corrupted in neural stem cells from older mice. By studying the Dbx2 gene we have shown that these changes may contribute to ageing in the brain by slowing the growth of brain stem cells and by switching on the activity of other age-associated genes.”

Co-lead scientist Dr Peter Rugg-Gunn at the Babraham Institute said: “Ageing ultimately affects all of us and the societal and healthcare burden of neurodegenerative diseases is enormous. By understanding how ageing affects the brain, at least in mice, we hope to identify ways to spot neural stem cell decline. Eventually, we may find ways to slow or even reverse brain deterioration – potentially by resetting the epigenetic switches – helping more of us to stay mentally agile for longer into old age.”

Co-lead scientist Dr Emanuele Cacci at Sapienza University said: “We hope this research will lead to benefits for human health. We have succeeded in accelerating parts of the ageing process in neural stem cells. By studying these genes more closely, we now plan to try turning back the clock for older cells. If we can do this in mice, then the same thing could also be possible for humans.”

This article has been republished from materials provided by the Babraham Institute. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Lupo, G., Nisi, P. S., Esteve, P., Paul, Y.-L., Novo, C. L., Sidders, B., … Rugg-Gunn, P. J. (n.d.). Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline. Aging Cell, n/a-n/a.


A single genetic mutation may increase a person’s risk of developing a rare, severe form of multiple sclerosis (MS) by roughly 60 percent, according to a study published recently in the journal Neuron.

That’s an unusually straightforward result for a complex disease like MS, which has previously been traced to hundreds of mutations that each increases the risk of developing the disease only slightly.

“That’s why our finding is unprecedented,” Carles Vilariño-Güell, Ph.D., an assistant professor of medical genetics at The University of British Columbia and one of the paper’s senior authors, told Healthline.

His team found the mutation by combing through a database of Canadians with MS who had donated blood samples as part of the Canadian Collaborative Project on Genetic Susceptibility to MS.

Some of these samples belonged to a family that was disproportionately diagnosed with the disease. Four first cousins and two parents developed MS.

The team isolated a common mutation from their DNA, and looked for that mutation in other individuals in the database.

That’s how they found a second family similarly afflicted. Three first cousins and two parents were diagnosed with MS.

Having so many cases of MS within a family is rare. The disease is not considered truly heritable, although a person’s risk does increase if a parent or sibling has the disease.

The families shared another rare trait. Most had the more severe version of the disease known as primary progressive MS, which makes up 10 to 15 percent of all MS cases.

Treatments for primary progressive MS have so far eluded scientists, although there are promising clinical trials underway of a drug called Ocrelizumab.

Future Research

The study found the mutation only in a handful of people, all of whom were diagnosed with a rare form of the disease.

Therefore, the researchers don’t suggest they have found the genetic basis of MS.

But they do think they’ve discovered a way to study how the disease progresses in the body and what drugs could be developed to slow or even stop it

Bruce Bebo, Ph.D., vice president of research at the National Multiple Sclerosis Society, agrees.

“Studying the genetics of a very rare form that is inherited can give us clues about pathways involved in MS in the general population,” he told Healthline.

The mutation appears to disable a regulatory gene called NR1H3, which codes for a protein that helps regulate the inflammation and the metabolism of lipids.

The researchers now plan to engineer a similar mutation in mice so they can study the outcome of a disabled NR1H3 gene and test potential new drugs in an animal model.

And because the NR1H3 pathway has already been implicated in diseases like atherosclerosis and heart disease, there are already drugs in clinical trials for safety that could be repurposed for treating MS, Vilariño-Güell said.

“Understanding the genetics of MS could help us get closer to individualizing therapy to people for better outcomes,” Bebo said.

Getting Personal with Treatment

People with a disease like MS, which appears in so many different ways and can be linked to so many different genetic components, could benefit by personalized medicine.

If the mechanism of each disease causing mutation or group of mutations is pinpointed, scientists could potentially design more effective, targeted treatments rather than the standard one-size-fits-all therapies.

That means tracking down the many different genetic hotspots that are linked to MS.

Overall, genetic predisposition accounts for only about a third of a person’s risk of developing the disease, Bebo said. Within that category only about half the genes responsible can be identified.

Researchers don’t know where the other half of that genetic risk comes from, Bebo said, but it makes sense that it would include rare mutations like this one that help explain risk in a small fraction of MS patients.

And there could be many different versions of these mutations.

“Odds are if you look at a different family the genetic risk would probably be something different than this,” Bebo said.

Speeding Through the Genome

The Canadian database has been available since the late 1990s, but only recently has the team had access to exome sequencing, a powerful, efficient tool that makes searching for tiny genetic changes easier.

This technique sequences only the DNA that codes for proteins — leaving the other 98 percent behind. It’s like speed reading the genome.

Exome sequencing has been particularly helpful for finding so-called “Mendelian” diseases — diseases that can be traced to a single, heritable mutation just like Gregor Mendel’s purple and white pea flowers. Cystic fibrosis and sickle cell anemia are two examples of these diseases.

With this discovery, the researchers say that have found a Mendelian form of MS.

That doesn’t mean the discovery won’t be beneficial for the 85 percent of people diagnosed with relapsing remitting MS. In many of those patients, the disease eventually changes course and becomes progressive.

Whatever is learned about primary progressive MS — a condition that doesn’t respond to treatments for other types of MS — could also potentially help those with secondary progressive MS, the researchers say.