Posts Tagged ‘DNA’

largest-ever-study-of-genetic-links-to-depression-and-anxiety-launched-309700

The NIHR and King’s College London are calling for 40,000 people diagnosed with depression or anxiety to enrol online for the Genetic Links to Anxiety and Depression (GLAD) Study and join the NIHR Mental Health Bioresource.

Researchers hope to establish the largest ever database of volunteers who can be called up to take part in research exploring the genetic factors behind the two most common mental health conditions – anxiety and depression.

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The GLAD study will make important strides towards better understanding of these disorders and provide a pool of potential participants for future studies, reducing the time-consuming process of recruiting patients for research.

Research has shown 30-40% of the risk for both depression and anxiety is genetic and 60-70% due to environmental factors. Only by having a large, diverse group of people available for studies will researchers be able to determine how genetic and environmental triggers interact to cause anxiety and depression.

Leader of the GLAD study and the NIHR Mental Health BioResource, Dr Gerome Breen of King’s College London, said: “It’s a really exciting time to become involved in mental health research, particularly genetic research which has made incredible strides in recent years – we have so far identified 46 genetic links for depression and anxiety.

“By recruiting 40,000 volunteers willing to be re-contacted for research, the GLAD Study will take us further than ever before. It will allow researchers to solve the big unanswered questions, address how genes and environment act together and help develop new treatment options.”

The GLAD Study, a collaboration between the NIHR BioResource and King’s College London, has been designed to be particularly accessible, with a view to motivating more people to take part in mental health research.

Research psychologist and study lead Professor Thalia Eley, King’s College London, said: “We want to hear from all different backgrounds, cultures, ethnic groups and genders, and we are especially keen to hear from young adults. By including people from all parts of the population, what we learn will be relevant to everyone. This is a unique opportunity to participate in pioneering medical science.”

https://www.nihr.ac.uk/news/nihr-launches-largest-ever-study-of-genetic-links-to-depression-and-anxiety/9201

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Human sperm, artwork

Half-siblings conceived with donated sperm and eggs are connecting online using DNA testing and online registries, forming extraordinarily large genetic families with dozens to hundreds of children linked to one parent, The Washington Post reports.

The modern family ties and genetic sleuthing are making it easier for donor-conceived children to learn about their backgrounds—and harder for anonymous donors to maintain anonymity. That has clearly been proven in tragic cases in which fertility doctors misled patients about their donor’s identity, even using their own sperm to sire dozens of children. But in legal, less-scandalous cases, the online connections are also highlighting the complex consequences of America’s lax regulations of the fertility industry, particularly on sperm and egg donations.

Many other countries have set legal limits on the number of children, families, or pregnancies to which one donor can contribute. Sperm donors in Taiwan can only sire one child, for instance. In Britain, they can donate to 10 families, and in China they can provide starter material for five pregnancies. But in the US, no such limits exist.

The nonprofit organization the American Society of Reproductive Medicine recommends limiting each sperm donor’s contributions to 25 births within a population of 800,000, which is about the size of San Francisco. As the Post points out, that could allow for one donor to sire more than 10,000 children across the entire country.

Though that number may seem absurdly large, the real numbers are also eye-popping. In one instance, half-siblings used online registries and DNA testing to discover that their biological father, sperm donor #2757, sired at least 29 girls and 16 boys. The half-siblings range in ages from 1 to 21 and live in eight states and four countries. Other sibling networks linked online ranged in size from dozens to nearly 200.

Such large genetic families raise concerns about half-siblings meeting unknowingly, falling in love, and having children of their own, risking genetic disorders. The vast family connections also exacerbate concerns that donors are often not required to provide medical histories and updates. There are already cases in the medical literature of half-siblings discovering each other while seeking treatments for rare genetic conditions, the Post points out.

Last month, the US Food and Drug Administration rejected a petition put forth by donor-offspring that sought to limit the number of births to which a donor could contribute. The petition also urged the FDA to track the number of each donor’s offspring and make collecting donor medical histories and updates mandatory. The FDA responded by saying that such oversight extended beyond its authority, which for now is limited to making sure that donors are screened for certain infectious diseases.

The response has infuriated families with donor-conceived children who want more regulations and transparency for donors. Meanwhile, donor-offspring continue to link up online. One daughter of donor #2757 told the Post:

“Every time I find a new sibling, I get anxiety and think to myself: when is it going to end?”

https://arstechnica.com/science/2018/09/sperm-donor-2757-sired-at-least-45-kids-now-theyre-connecting-online/

Methyl chemical groups dot lengths of DNA, helping to control when certain genes are accessible by a cell. In new research, UCLA scientists have shown that at the connections between brain cells—which often are located far from the central control centers of the cells—methyl groups also dot chains of RNA. This methyl markup of RNA molecules is likely key to brain cells’ ability to quickly send signals to other cells and react to changing stimuli in a fraction of a second.

To dictate the biology of any cell, DNA in the cell’s nucleus must be translated into corresponding strands of RNA. Next, the messenger RNA, or mRNA—an intermediate genetic molecule between DNA and proteins—is transcribed into proteins. If a cell suddenly needs more of a protein—to adapt to an incoming signal, for instance—it must translate more DNA into mRNA. Then it must make more proteins and shuttle them through the cell to where they are needed. This process means that getting new proteins to a distant part of a cell, like the synapses of neurons where signals are passed, can take time.

Research has recently suggested that methyl chemical groups, which can control when DNA is transcribed into mRNA, are also found on strands of mRNA. The methylation of mRNA, researchers hypothesize, adds a level of control to when the mRNA can be translated into proteins, and their occurrence has been documented in a handful of organs throughout the bodies of mammals. The pattern of methyls on mRNA in any given cell is dubbed the “epitranscriptome.”

UCLA and Kyoto University researchers mapped out the location of methyls on mRNA found at the synapses, or junctions, of mouse brain cells. They isolated brain cells from adult mice and compared the epitranscriptome found at the synapses to the epitranscriptomes of mRNA elsewhere in the cells. At more than 4,000 spots on the genome, the mRNA at the synapse was methylated more often. More than half of these spots, the researchers went on to show, are in genes that encode proteins found mostly at the synapse. The researchers found that when they disrupted the methylation of mRNA at the synapse, the brain cells didn’t function normally.

The methylation of mRNA at the synapse is likely one of many ways that neurons speed up their ability to send messages, by allowing the mRNA to be poised and ready to translate into proteins when needed.

The levels of key proteins at synapses have been linked to a number of psychiatric disorders, including autism. Understanding how the epitranscriptome is regulated, and what role it plays in brain biology, may eventually provide researchers with a new way to control the proteins found at synapses and, in turn, treat disorders characterized by synaptic dysfunction.

More information: Daria Merkurjev et al. Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0173-6

Read more at: https://phys.org/news/2018-08-methyl-rna-key-brain-cell.html#jCp

by CAROLYN Y. JOHNSON

In 1959, Soviet scientists embarked on an audacious experiment to breed a population of tame foxes, a strain of animals that wouldn’t be aggressive or fearful of people.

Scientists painstakingly selected the friendliest foxes to start each new generation, and within 10 cycles they began to see differences from wild foxes – fox pups that wagged their tails eagerly at people or with ears that stayed folded like a dog’s.

This study in animal domestication, known as the Russian farm-fox experiment, might be just a fascinating historical footnote – a quirky corner in the otherwise fraught scientific heritage of Soviet Russia.

Instead, it spawned an ongoing area of research into how domestication, based purely on behavioral traits, can result in other changes – like curlier tails and changes to fur color.

Now, the tools of modern biology are revealing the genetic changes that underpin the taming of foxes of Siberia.

In a new study, published Monday in Nature Ecology & Evolution, scientists used genome sequencing to identify 103 stretches of the fox genome that appear to have been changed by breeding, a first pass at identifying the genes that make some foxes comfortable with humans and others wary and aggressive.

The scientists studied the genomes of 10 foxes from three different groups: the tame population, a strain that was bred to be aggressive toward people and a conventional group bred to live on a farm.

Having genetic information from all three groups allowed the researchers to identify regions of the genome that were likely to have changed due to the active selection of animals with different behaviors, rather than natural fluctuation over time.

Those regions offer starting points in efforts to probe the genetic basis and evolution of complex traits, such as sociability or aggressiveness.

“The experiment has been going on for decades and decades, and to finally have the genome information, you get to look and see where in the genome and what in the genome has been likely driving these changes that we’ve seen – it’s a very elegant experimental design,” said Adam Boyko, an associate professor of biomedical sciences at Cornell University, who was not involved in the study.

While some genetic traits are relatively simple to unravel, the underpinnings of social behaviors aren’t easy to dissect. Behavior is influenced by hundreds or thousands of genes, as well as the environment – and typically behaviors fall on a wide spectrum.

The existence of fox populations bred solely for how they interact with people offers a rare opportunity to strip away some of the other complexity – with possible implications for understanding such traits in people and other animals, too, since evolution may work on the same pathways or even the same genes.

“We’re interested to see what are the genes that make such a big difference in behavior. There are not so many animal models which are good to study genetics of social behavior, and in these foxes it’s such a big difference between tame foxes compared to conventional foxes, and those selected for aggressive behavior,” said Anna Kukekova, an assistant professor at the University of Illinois at Urbana-Champaign, who led the work.

Kukekova and colleagues began studying one very large gene that they think may be linked to tame behavior, called SorCS1. The gene plays a role in sorting proteins that allow brain cells to communicate.

Kukekova is interested in determining what happens if the gene is deleted in a mouse and to search for specific mutations that might contribute to differences in behavior.

Bridgett vonHoldt, an assistant professor of ecology and evolutionary biology at Princeton University, said changes that occurred in foxes “overlap extensively with those observed in the transition of gray wolves to modern domestic dogs.”

She said the study may help dog and fox biologists determine if there are complex behavioral traits under the control of just a few genes.

Recent fox evolution in a domesticated population may seem to have little to do with understanding the genetics of human behavior, but interest in domestication has grown as an area of scientific interest in part because genes involved in behavior in one animal may play a similar role in another.

“One reason why it is interesting is it gives us some insights about us. Humans are domesticated themselves, in a way,” Boyko said.

“We’re much more tolerant of being around other humans than probably we were as we were evolving; we’ve had to undergo a transformation, even relatively recently from the agricultural revolution.”

https://www.sciencealert.com/soviet-era-fox-taming-experiment-may-reveal-genes-behind-social-behavior

by PETER DOCKRILL

The appearance of wrinkled, weathered skin and the disappearance of hair are two of the regrettable hallmarks of getting older, but new research suggests these physical manifestations of ageing might not be permanent – and can potentially be reversed.

New experiments with mice show that by treating a mutation-based imbalance in mitochondrial function, animals that looked physically aged regrew hair and lost their wrinkles – restoring them to a healthy, youthful appearance in just weeks.

“To our knowledge, this observation is unprecedented,” says geneticist Keshav Singh from the University of Alabama at Birmingham.

One of the focal points of anti-ageing research is investigating the so-called mitochondrial theory of ageing, which posits that mutations in the DNA of our mitochondria – the ‘powerhouse of the cell’ – contribute over time to defects in these organelles, giving rise to ageing itself, associated chronic diseases, and other human pathologies.

To investigate these mechanisms, Singh and fellow researchers genetically modified mice to have depleted mitochondrial DNA (mtDNA).

They did this by adding the antibiotic doxycycline to the food and drinking water of transgenic mice. This turned on a mutation which causes mitochondrial dysfunction and depletes their healthy levels of mtDNA.

In the space of eight weeks, the previously healthy mice developed numerous physical changes reminiscent of natural ageing: greying and significantly thinning hair, wrinkled skin, along with slowed movements and lethargy.

The depleted mice also showed an increased numbers of skin cells, contributing to an abnormal thickening of the outer layer of their skin, in addition to dysfunctional hair follicles, and an imbalance between enzymes and inhibitors that usually prevents collagen fibres from wrinkling skin.

But once the doxycycline was no longer fed to the animals, and their mitochondria could get back to doing what they do best, the mice regained their healthy, youthful appearance within just four weeks.

Effectively, they reverted to the animals they were before their mitochondrial DNA content was tampered with – which could mean mitochondria are reversible regulators of skin ageing and hair loss.

“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype,” says Singh.

“Further experiments are required to determine whether phenotypic changes in other organs can also be reversed to wildtype level by restoration of mitochondrial DNA.”

Even though the mitochondrial depletion affected the entire animal, for the most part the induced mutation did not seem to greatly affect other organs – suggesting hair and skin tissue are most susceptible to the depletion.

But it could also mean the discovery here isn’t the fountain of youth for slowing or reversing the wider physiological causes of ageing – only its more surface, cosmetic symptoms. Although, at least some in the scientific community aren’t persuaded yet.

“While this is a clever proof of principle, I am not convinced of the clinical relevance of this,” biologist Lindsay Wu, from the Laboratory for Ageing Research at the University of New South Wales, who was not involved in the study, told ScienceAlert.

“The rate of mitochondrial DNA mutations here is many orders of magnitude higher than the rate of mitochondrial DNA mutations observed during normal ageing.”

“I would be really keen to see what happens when they turn down the rate of mutations to a lower level more relevant to normal ageing,” Wu added.

In that vein – with further research, and assuming these effects can be replicated outside the bodies of mice, which isn’t yet known – it’s possible this could turn out to be a major discovery in the field.

For their part, at least, the researchers are convinced mtDNA mutations can teach us a lot more about how the clocks in our bodies might be stopped (or wound back to another time entirely).

“This mouse model should provide an unprecedented opportunity for the development of preventative and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of ageing-associated skin and hair pathology,” the authors write in their paper, “and other human diseases in which mitochondrial dysfunction plays a significant role.”

The findings are reported in Cell Death and Disease.

https://www.sciencealert.com/unprecedented-dna-discovery-actually-reverses-wrinkles-and-hair-loss-mitochondria-mutation-mtdna

Scientists have revealed a new link between alcohol, heart health and our genes.

The researchers investigated faulty versions of a gene called titin which are carried by one in 100 people or 600,000 people in the UK.

Titin is crucial for maintaining the elasticity of the heart muscle, and faulty versions are linked to a type of heart failure called dilated cardiomyopathy.

Now new research suggests the faulty gene may interact with alcohol to accelerate heart failure in some patients with the gene, even if they only drink moderate amounts of alcohol.

The research was carried out by scientists from Imperial College London, Royal Brompton Hospital, and MRC London Institute of Medical Sciences, and published this week in the latest edition of the Journal of the American College of Cardiology.

The study was supported by the Department of Health and Social Care and the Wellcome Trust through the Health Innovation Challenge Fund.

In the first part of the study, the team analysed 141 patients with a type of heart failure called alcoholic cardiomyopathy (ACM). This condition is triggered by drinking more than 70 units a week (roughly seven bottles of wine) for five years or more. In severe cases the condition can be fatal, or leave patients requiring a heart transplant.

The team found that the faulty titin gene may also play a role in the condition. In the study 13.5 per cent of patients were found to carry the mutation – much higher than the proportion of people who carry them in the general population.

These results suggest this condition is not simply the result of alcohol poisoning, but arises from a genetic predisposition – and that other family members may be at risk too, explained Dr James Ware, study author from the National Heart and Lung Institute at Imperial.

“Our research strongly suggests alcohol and genetics are interacting – and genetic predisposition and alcohol consumption can act together to lead to heart failure. At the moment this condition is assumed to be simply due to too much alcohol. But this research suggests these patients should also be checked for a genetic cause – by asking about a family history and considering testing for a faulty titin gene, as well as other genes linked to heart failure,” he said.

He added that relatives of patients with ACM should receive assessment and heart scans – and in some cases have genetic tests – to see if they unknowingly carry the faulty gene.

In a second part of the study, the researchers investigated whether alcohol may play a role in another type of heart failure called dilated cardiomyopathy (DCM). This condition causes the heart muscle to become stretched and thin, and has a number of causes including viral infections and certain medications. The condition can also be genetic, and around 12 per cent of cases of DCM are thought to be linked to a faulty titin gene.

In the study the team asked 716 patients with dilated cardiomyopathy how much alcohol they consumed.

None of the patients consumed the high-levels of alcohol needed to cause ACM. But the team found that in patients whose DCM was caused by the faulty titin gene, even moderately increased alcohol intake (defined as drinking above the weekly recommended limit of 14 units), affected the heart’s pumping power.

Compared to DCM patients who didn’t consume excess alcohol (and whose condition wasn’t caused by the faulty titin gene), excess alcohol was linked to reduction in heart output of 30 per cent.

More research is now needed to investigate how alcohol may affect people who carry the faulty titin gene, but do not have heart problems, added Dr Paul Barton, study co-author from the National Heart and Lung Institute at Imperial:

“Alcohol and the heart have a complicated relationship. While moderate levels may have benefits for heart health, too much can cause serious cardiac problems. This research suggests that in people with titin-related heart failure, alcohol may worsen the condition.

“An important wider question is also raised by the study: do mutations in titin predispose people to heart failure when exposed to other things that stress the heart, such as cancer drugs or certain viral infections? This is something we are actively seeking to address.”

The research was supported by the Department of Health and Social Care and Wellcome Trust through the Health Innovation Challenge Fund, the Medical Research Council, the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and the British Heart Foundation.

Reference: Ware, J. S., Amor-Salamanca, A., Tayal, U., Govind, R., Serrano, I., Salazar-Mendiguchía, J., … Garcia-Pavia, P. (2018). Genetic Etiology for Alcohol-Induced Cardiac Toxicity. Journal of the American College of Cardiology, 71(20), 2293–2302. https://doi.org/10.1016/j.jacc.2018.03.462

https://www.technologynetworks.com/genomics/news/faulty-gene-leads-to-alcohol-induced-heart-failure-304365?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=63228690&_hsenc=p2ANqtz-9oqDIw3te1NPoj51s94kxnA1ClK8Oiecfela6I4WiITEbm_-SWdmw6pjMTwm2YP24gqSzRaBvUK1kkb2kZEJKPcL5JtQ&_hsmi=63228690

Prof Neil Gemmell, a New Zealand scientist leading the project, said he did not believe in Nessie, but was confident of finding genetic codes for other creatures.

He said a “biological explanation” might be found to explain some of the stories about the Loch Ness Monster.

The team will collect tiny fragments of skin and scales for two weeks in June.

Prof Gemmell, from the University of Otago in Dunedin, said: “I don’t believe in the idea of a monster, but I’m open to the idea that there are things yet to be discovered and not fully understood.

“Maybe there’s a biological explanation for some of the stories.”

The University of the Highlands and Islands’ UHI Rivers and Lochs Institute in Inverness is assisting in the project.

Other organisms

After the research team’s trip to Loch Ness, the samples will be sent to laboratories in New Zealand, Australia, Denmark and France to be analysed against a genetic database.

Prof Gemmell said: “There’s absolutely no doubt that we will find new stuff. And that’s very exciting.

“While the prospect of looking for evidence of the Loch Ness monster is the hook to this project, there is an extraordinary amount of new knowledge that we will gain from the work about organisms that inhabit Loch Ness – the UK’s largest freshwater body.”

The scientist said the team expected to find sequences of DNA from plants, fish and other organisms.

He said it would be possible to identify these plants and animals by comparing the sequences of their DNA against sequences held on a large, international database.

Prof Gemmell added: “There is this idea that an ancient Jurassic Age reptile might be in Loch Ness.

“If we find any reptilian DNA sequences in Loch Ness, that would be surprising and would be very, very interesting.”

The Loch Ness Monster is one of Scotland’s oldest and most enduring myths. It inspires books, TV shows and films, and sustains a major tourism industry around its home.

The story of the monster can be traced back 1,500 years when Irish missionary St Columba is said to have encountered a beast in the River Ness in 565AD.

Later, in the 1930s, The Inverness Courier reported the first modern sighting of Nessie.

Whale-like creature

In 1933, the newspaper’s Fort Augustus correspondent, Alec Campbell, reported a sighting by Aldie Mackay of what she believed to be Nessie.

Mr Campbell’s report described a whale-like creature and the loch’s water “cascading and churning”.

The editor at the time, Evan Barron, suggested the beast be described as a “monster”, kick starting the modern myth of the Loch Ness Monster.

Over the years various efforts have tried and failed to find the beast.

In tourism terms, there are two exhibitions dedicated to the monster and there is not a tourist shop in the Highlands, and even more widely across Scotland, where a cuddly toy of Nessie cannot be found.

In 2016, the inaugural Inverness Loch Ness International Knitting Festival exhibited knitted Nessie’s made from all parts of the world.

‘Record high’

In popular culture, the Loch Ness Monster has reared its head many times, including in 1975’s four-part Doctor Who – Terror of the Zygons, the 1980s cartoon The Family-Ness as well as The Simpsons and 1996’s Loch Ness starring Ted Danson.

In 2014, it was reported that for the first time in almost 90 years no “confirmed sightings” had been made of the Loch Ness Monster.

Gary Campbell, who keeps a register of sightings, said no-one had come forward in 18 months to say they had seen the monster.

But last year, sightings hit a record high.

http://www.bbc.com/news/uk-scotland-highlands-islands-44223259