探花直播 of Cambridge - DNA

Back to BRCA: the discovery of a breast cancer risk gene

cjb250 — Mon, 07 Oct 2024 08:00:50 +0000

In 1994, a landmark paper identified a gene 鈥� BRCA1 鈥� that significantly increases the risk of breast and ovarian cancers when faulty. Thirty years on, we look at the major impact it has had on how we understand and treat cancer 鈥� and why there is still much to learn.

Genetics study points to potential treatments for restless leg syndrome

cjb250 — Wed, 05 Jun 2024 09:00:25 +0000

Restless leg syndrome can cause an unpleasant crawling sensation in the legs and an overwhelming urge to move them. Some people experience the symptoms only occasionally, while others get symptoms every day. Symptoms are usually worse in the evening or at night-time and can severely impair sleep.

Despite the condition being relatively common 鈥� up to one in 10 older adults experience symptoms, while 2-3% are severely affected and seek medical help 鈥� little is known about its causes. People with restless leg syndrome often have other conditions, such as depression or anxiety, cardiovascular disorders, hypertension, and diabetes, but the reason why is not known.

Previous studies had identified 22 genetic risk loci 鈥� that is, regions of our genome that contain changes associated with increased risk of聽 developing the condition. But there are still no known 鈥榖iomarkers鈥� 鈥� such as genetic signatures 鈥� that could be used to objectively diagnose the condition.

To explore the condition further, an international team led by researchers at the Helmholtz Munich Institute of Neurogenomics, Institute of Human Genetics of the Technical 探花直播 of Munich (TUM) and the 探花直播 of Cambridge pooled and analysed data from three genome-wide association studies. These studies compared the DNA of patients and healthy controls to look for differences more commonly found in those with restless leg syndrome. By combining the data, the team was able to create a powerful dataset with more than 100,000 patients and over 1.5 million unaffected controls.

探花直播results of the study are published today in Nature Genetics.

Co-author Dr Steven Bell from the 探花直播 of Cambridge said: 鈥淭his study is the largest of its kind into this common 鈥� but poorly understood 鈥� condition. By understanding the genetic basis of restless leg syndrome, we hope to find better ways to manage and treat it, potentially improving the lives of many millions of people affected worldwide.鈥�

探花直播team identified over 140 new genetic risk loci, increasing the number known eight-fold to 164, including three on the X chromosome. 探花直播researchers found no strong genetic differences between men and women, despite the condition being twice as common in women as it is men 鈥� this suggests that a complex interaction of genetics and the environment (including hormones) may explain the gender differences we observe in real life.

Two of the genetic differences identified by the team involve genes known as glutamate receptors 1 and 4 respectively, which are important for nerve and brain function. These could potentially be targeted by existing drugs, such as anticonvulsants like perampanel and lamotrigine, or used to develop new drugs. Early trials have already shown positive responses to these drugs in patients with restless leg syndrome.

探花直播researchers say it would be possible to use basic information like age, sex, and genetic markers to accurately rank who is more likely to have severe restless leg syndrome in nine cases out of ten.

To understand how restless leg syndrome might affect overall health, the researchers used a technique called Mendelian randomisation. This uses genetic information to examine cause-and-effect relationships. It revealed that the syndrome increases the risk of developing diabetes.

Although low levels of iron in the blood are thought to trigger restless leg syndrome 鈥� because they can lead to a fall in the neurotransmitter dopamine 鈥� the researchers did not find strong genetic links to iron metabolism. However, they say they cannot completely rule it out as a risk factor.

Professor Juliane Winkelmann from TUM, one of senior authors of the study, said: 鈥淔or the first time, we have achieved the ability to predict restless leg syndrome risk. It has been a long journey, but now we are empowered to not only treat but even prevent the onset of this condition in our patients.鈥�

Professor Emanuele Di Angelantonio, a co-author of the study and Director of the NIHR and NHS Blood and Transplant-funded Research Unit in Blood Donor Health and Behaviour, added: "Given that low iron levels are thought to trigger restless leg syndrome, we were surprised to find no strong genetic links to iron metabolism in our study.聽It may be that the relationship is more complex than we initially thought, and further work is required."

探花直播dataset included the INTERVAL study of England鈥檚 blood donors in collaboration with NHS Blood and Transplant.

A full list of funders can be found in the study paper.

Reference
Schormair et al. Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology, and risk prediction. Nature Genetics; 5 June 2024; DOI: 10.1038/s41588-024-01763-1

Scientists have discovered genetic clues to the cause of restless leg syndrome, a condition common among older adults. 探花直播discovery could help identify those individuals at greatest risk of the condition and point to potential ways to treat it.

By understanding the genetic basis of restless leg syndrome, we hope to find better ways to manage and treat it, potentially improving the lives of many millions of people affected worldwide

Steven Bell

DANNY G

Woman covered with white blanket

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways 鈥� on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cancer's climate innovation

plc32 — Thu, 04 Apr 2024 16:10:38 +0000

An enzyme inspired by brain cancer DNA that has the potential to slash greenhouse gas emissions from the production of nylon won the 2024 Cambridge Climate Challenge.

Largest genetic study of brain structure identifies how the brain is organised

cjb250 — Thu, 17 Aug 2023 15:00:47 +0000

Our brains are very complex organs, with huge variety between individuals in terms of the overall volume of the brain, how it is folded and how thick these folds are. Little is known about how our genetic make-up shapes the development of the brain.

To answer this question, a team led by researchers at the Autism Research Centre, 探花直播 of Cambridge, accessed MRI scans from over 32,000 adults from the UK Biobank cohort and over 4,000 children from the US-based ABCD study. From these scans, the researchers measured multiple properties of the outermost layer of the brain called the cortex. These included measures of the area and volume of the cortex as well as how the cortex is folded.

They then linked these properties, measured both across the entire cortex as well as in 180 individual regions of the cortex, to genetic information across the genome. 探花直播team identified over 4,000 genetic variants linked to brain structure.

These findings have allowed researchers to confirm and, in some cases, identify, how different properties of the brain are genetically linked to each other.

Dr Varun Warrier from the Autism Research Centre, who co-led the study, said: 鈥淥ne question that has interested us for a while is if the same genes that are linked to how big the cortex is 鈥� measured as both volume and area 鈥� are also linked to how the cortex is folded. By measuring these different properties of the brain and linking them to genetics, we found that different sets of genes contribute to folding and size of the cortex.鈥�

探花直播team also checked whether the same genes that are linked to variation in brain size in the general population overlap with genes linked to clinical conditions where head sizes are much larger or smaller than the general population, known as cephalic conditions.

Dr Richard Bethlehem, also from the Autism Research Centre and a co-lead of the study, said: 鈥淢any of the genes linked with differences in the brain sizes in the general population overlapped with genes implicated in cephalic conditions. However, we still do not know how exactly these genes lead to changes in brain size.鈥�

Dr Warrier added: 鈥淭his work shows that how our brain develops is partly genetic. Our findings can be used to understand how changes in the shape and size of the brain can lead to neurological and psychiatric conditions, potentially leading to better treatment and support for those who need it.鈥�

This study was supported by the Wellcome Trust. It was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust, and the NIHR Cambridge Biomedical Research Centre.

Reference
Warrier, V et al. Genetic insights into human cortical organisation and development through genome-wide analyses of 2,347 neuroimaging phenotypes. Nat Gen; 17 Aug 2023; DOI: 10.1038/s41588-023-01475-y

探花直播largest ever study of the genetics of the brain 鈥� encompassing some 36,000 brain scans 鈥� has identified more than 4,000 genetic variants linked to brain structure. 探花直播results of the study, led by researchers at the 探花直播 of Cambridge, are published in Nature Genetics.

Our findings can be used to understand how changes in the shape and size of the brain can lead to neurological and psychiatric conditions, potentially leading to better treatment and support for those who need it

Varun Warrier

holdendrils

Illustration of brain anatomy

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified.聽 All rights reserved. We make our image and video content available in a number of ways 鈥� as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Largest ever DNA and health research programme for children and young people launches

Anonymous — Tue, 25 Jul 2023 00:00:22 +0000

探花直播National Institute for Health and Care Research (NIHR) BioResource鈥檚 D-CYPHR 鈥� the DNA, Children and Young People鈥檚 Health Resource 鈥� will play a key role in pioneering new treatments and creating better care for children and the adults they will become 鈥� everything from improving understanding of mental health to combatting heart disease.聽探花直播programme is led by NIHR BioResource in partnership with the NHS, Anna Freud and the 探花直播 of Cambridge.聽聽聽聽聽

Many serious health conditions start in the first two decades of life, with over 1.7 million children in England alone suffering from long-term health conditions. However, most health research is carried out with adults, meaning we are not only missing important opportunities to understand how disease starts, develops and its causes, but are limited in developing new treatments.聽聽

Dr Anna Moore, 探花直播 of Cambridge, clinical lead for D-CYPHR, said: 鈥淭oday we are at the beginning of the most tremendous opportunity which will transform our understanding of genetics for children's health: a moment where families can help much needed health research from home. This will boost all the amazing research happening across the UK.鈥�

探花直播ground-breaking new programme is open to any child and young person aged 0 to 15 in the UK, to create the biggest health initiative of its kind in this country and a world first 鈥� a new national childhood DNA health resource for research from birth through adolescence.聽聽

Supporting the programme鈥檚 launch, Dr Xand van Tulleken, BBC presenter, urged parents and their children to get involved:聽鈥淲e urgently need research projects that support children鈥檚 health and we need children to volunteer to help! Children are amazing 鈥� I鈥檓 constantly astounded by their bravery in stepping up for causes they believe in. Today, we鈥檙e offering the chance to be a hero for healthcare 鈥� just by spitting in a tube.

鈥淒-CYPHR will help future children, and it will help all of us in our adult lives. 探花直播ambition and scope of the D-CYPHR project is awe inspiring and it relies on these incredible volunteers to make amazing discoveries from which all of us, children and adults, will benefit.鈥澛�

Research has shown the power that understanding genetics can have on outcomes for a range of conditions and illness, from improvements to how diabetes is treated in children, to the national roll-out of whole genome sequencing for babies and children in intensive care. Understanding genetics is vital in helping to understand and treat illness.聽聽

D-CYPHR aims to support this, while also mapping development in children and young people. 探花直播environment and experiences while growing up work together with genetics to affect development, and the likelihood of getting diseases. 探花直播more we can understand about this, the more treatments can be developed, and tailored to individuals. It even opens up the opportunity for earlier identification of problems, and in the future, we hope to be able to avoid some illnesses, like heart disease and type II diabetes.聽

Dr Anna Moore continued: 鈥淲e鈥檝e carefully designed and piloted the programme alongside children, schools and families over two years. This has been very important as this project will also be a way to address inequality in health research 鈥� health research needs to benefit everyone, and so we need children and young people from all backgrounds to get involved.

鈥淓ach sample joins a resource with thousands of others showing how environment and genetics affect health. 探花直播potential of D-CYPHR is therefore massive. We鈥檙e excited to unlock these secrets together with the young heroes that are agreeing to help us.鈥澛�

Joining D-CYPHR is simple. Each young person, with parental consent, donates a saliva sample and answers a health and lifestyle questionnaire.聽探花直播information and sample are depersonalised and joins the resource. By studying thousands of DNA samples together with health information, scientists can begin to see the big picture of how our genes and our environment influence our health.

In a world first, the new D-CYPHR programme will support research into any health conditions that begin in or have their origins in childhood 鈥� not just a specific condition or age group. This will include mental health conditions, diabetes, heart conditions, rare diseases, immune conditions and many more. It will also help us understand childhood development and what sets the foundations for a healthy life.聽聽

Professor Lucy Chappell, Chief Executive of the NIHR commented: "We鈥檝e seen that genetics can help us unlock our understanding of diseases. Now we want to build on that knowledge by ensuring that our children and young people can access the power of genetics to transform diagnosis and treatment through this research. This exciting new project will help us develop an understanding of their genetics in a way that is more detailed and focused than ever before.鈥�

Secretary of State for Health and Social Care, Steve Barclay said: 鈥淭his pioneering genetic research programme is an exciting opportunity to advance our understanding of the causes of diseases and how they develop from childhood through to adulthood.

鈥淏y focusing on the DNA of children and young people we鈥檒l be able to track how genetics affect a child鈥檚 development and build a picture of what might impact on their future health. As a result we鈥檒l be able to develop more effective, bespoke treatments and even explore potential preventative measures for a wide range of conditions, including mental health issues and heart disease.鈥�

Find out how you can take part on the D-CYPHR website

Adapted from an NIHR press release

Cambridge researchers are helping launch a nationwide study for children and young people to unlock the power of our DNA.

Today we are at the beginning of the most tremendous opportunity which will transform our understanding of genetics for children's health

Anna Moore

Anna Samoylova

Children playing tug of war

Suzie, mother of a D-CYPHR participant from Salisbury

鈥淚 saw my daughter, Sophie's, journey from a very unwell newborn to a vibrant and active seven-year-old, enjoying life to the fullest. She鈥檚 now thriving and loves reading, baking, riding, and drama, which brings immense joy to her and our family. But in her early days, she faced significant health challenges. 探花直播cause of these episodes was unknown, leaving us puzzled and seeking medical answers. Some of these questions remain unanswered, and as a doctor, I know this can happen.

鈥淚f by taking part in D-CYPHR, and expanding medical knowledge, then someone else in a similar position gets a better understanding of a cause and so the right treatment, then it鈥檚 completely worth it. D-CYPHR is an opportunity for us to support research that might give answers to other parents in our situation, as well as create better treatments for millions of people.鈥澛�

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified.聽 All rights reserved. We make our image and video content available in a number of ways 鈥� as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Should we allow genome editing of human embryos?

cjb250 — Tue, 28 Feb 2023 13:39:24 +0000

A citizens鈥� jury of individuals whose lives have been affected by hereditary disease has voted in favour of asking the UK government to consider changing the law to allow genome editing of human embryos to treat serious genetic conditions.

DNA sequencing method lifts 鈥榲eil鈥� from genome black box

cr696 — Mon, 23 Jan 2023 16:00:00 +0000

In a paper published in the journal Nature Biotechnology, 探花直播 of Cambridge researchers have outlined a new DNA sequencing method that can detect where and how small molecule drugs interact with the targeted genome.

鈥淯nderstanding how drugs work in the body is essential to creating better, more effective therapies,鈥� said co-first author Dr Zutao Yu from the Yusuf Hamied Department of Chemistry. 鈥淏ut when a therapeutic drug enters a cancer cell with a genome that has three billion bases, it鈥檚 like entering a black box.鈥�

探花直播powerful method, called Chem-map, lifts the veil of this genomic black box by enabling researchers to detect where small molecule drugs interact with their targets on the DNA genome.

Each year, millions of cancer patients receive treatment with genome-targeting drugs, such as doxorubicin. But despite decades of clinical use and research, the molecular mode of action with the genome is still not well-understood.

鈥淟ots of life-saving drugs directly interact with DNA to treat diseases such as cancer,鈥� said co-first author Dr Jochen Spiegel. 鈥淥ur new method can precisely map where drugs bind to the genome, which will help us to develop better drugs in the future.鈥�

Chem-map allows researchers to conduct in situ mapping of small molecule-genome interactions with unprecedented precision, by using a strategy called small-molecule-directed transposase Tn5 tagmentation. This detects the binding site in the genome where a small molecule binds to genomic DNA or DNA-associated proteins.

In the study, the researchers used Chem-map to determine the direct binding sites in human leukaemia cells of the widely used anticancer drug doxorubicin. 探花直播technique also showed how the combined therapy of using doxorubicin on cells already exposed to the histone deacetylase (HDAC) inhibitor tucidinostat could have a potential clinical advantage.

探花直播technique was also used to map the binding sites of certain molecules on DNA G-quadruplexes, known as G4s. G4s are four-stranded secondary structures that have been implicated in gene regulation, and could be possible targets for future anti-cancer treatments.

鈥淚 am so proud that we have been able to solve this longstanding problem 鈥� we have established a highly efficient approach which will open many paths for new research,鈥� said Yu.

Professor Sir Shankar Balasubramanian, who led the research, said: 鈥淐hem-map is a powerful new method to detect the site in the genome where a small molecule binds to DNA or DNA-associated proteins. It provides enormous insights on how some drug therapies interact with the human genome, and makes it easier to develop more effective and safer drug therapies.鈥�

Reference:
Zutao Yu,聽Jochen Spiegel et al. 'Chem-map profiles drug binding to chromatin in cells.' Nature Biotechnology (2023). DOI:聽10.1038/s41587-022-01636-0

Many life-saving drugs directly interact with DNA to treat diseases such as cancer, but scientists have struggled to detect how and why they work 鈥� until now.

KTSDESIGN/SCIENCE PHOTO LIBRARY via Getty Images

Illustration of DNA molecules

探花直播text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified.聽 All rights reserved. We make our image and video content available in a number of ways 鈥� as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Gone fishing: highly accurate test for common respiratory viruses uses DNA as 鈥榖ait鈥�

sc604 — Mon, 16 Jan 2023 16:00:00 +0000

探花直播test uses DNA 鈥榥anobait鈥� to detect the most common respiratory viruses 鈥� including influenza, rhinovirus, RSV and COVID-19 鈥� at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. 探花直播results are reported in the journal Nature Nanotechnology.

探花直播winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

鈥淢any respiratory viruses have similar symptoms but require different treatments: we wanted to see if we could search for multiple viruses in parallel,鈥� said Filip Bo拧kovi膰 from Cambridge鈥檚 Cavendish Laboratory, the paper鈥檚 first author. 鈥淎ccording to the World Health Organization, respiratory viruses are the cause of death for 20% of children who die under the age of five. If you could come up with a test that could detect multiple viruses quickly and accurately, it could make a huge difference.鈥�

For Bo拧kovi膰, the research is also personal: as a young child, he was in hospital for almost a month with a high fever. Doctors could not figure out the cause of his illness until a PCR machine became available.

鈥淕ood diagnostics are the key to good treatments,鈥� said Bo拧kovi膰, who is a PhD student at St John鈥檚 College, Cambridge. 鈥淧eople show up at hospital in need of treatment and they might be carrying multiple different viruses, but unless you can discriminate between different viruses, there is a risk patients could receive incorrect treatment.鈥�

PCR tests are powerful, sensitive and accurate, but they require a piece of genome to be copied millions of times, which takes several hours.

探花直播Cambridge researchers wanted to develop a test that uses RNA to detect viruses directly, without the need to copy the genome, but with high enough sensitivity to be useful in a healthcare setting.

鈥淔or patients, we know that rapid diagnosis improves their outcome, so being able to detect the infectious agent quickly could save their life,鈥� said co-author Professor Stephen Baker, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease. 鈥淔or healthcare workers, such a test could be used anywhere, in the UK or in any low- or middle-income setting, which helps ensure patients get the correct treatment quickly and reduce the use of unwarranted antibiotics.鈥�

探花直播researchers based their test on structures built from double strands of DNA with overhanging single strands. These single strands are the 鈥榖ait鈥�: they are programmed to 鈥榝ish鈥� for specific regions in the RNA of target viruses. 探花直播nanobaits are then passed through very tiny holes called nanopores. Nanopore sensing is like a ticker tape reader that transforms molecular structures into digital information in milliseconds. 探花直播structure of each nanobait reveals the target virus or its variant.

探花直播researchers showed that the test can easily be reprogrammed to discriminate between viral variants, including variants of the virus that causes COVID-19. 探花直播approach enables near 100% specificity due to the precision of the programmable nanobait structures.

鈥淭his work elegantly uses new technology to solve multiple current limitations in one go,鈥� said Baker. 鈥淥ne of the things we struggle with most is the rapid and accurate identification of the organisms causing the infection. This technology is a potential game-changer; a rapid, low-cost diagnostic platform that is simple and can be used anywhere on any sample.鈥�

A patent on the technology has been filed by Cambridge Enterprise, the 探花直播鈥檚 commercialisation arm, and co-author Professor Ulrich Keyser has co-founded a company, Cambridge Nucleomics, focused on RNA detection with single-molecule precision.

鈥淣anobait is based on DNA nanotechnology and will allow for many more exciting applications in the future,鈥� said Keyser, who is based at the Cavendish Laboratory. 鈥淔or commercial applications and roll-out to the public we will have to convert our nanopore platform into a hand-held device.鈥�

鈥淏ringing together researchers from medicine, physics, engineering and chemistry helped us come up with a truly meaningful solution to a difficult problem,鈥� said Bo拧kovi膰, who received a 2022 PhD award from Cambridge Society for Applied Research for this work.

探花直播research was supported in part by the European Research Council, the Winton Programme for the Physics of Sustainability, St John鈥檚 College, UK Research and Innovation (UKRI), Wellcome, and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Reference:
Filip Bo拧kovi膰 et al. 鈥�Simultaneous identification of viruses and viral variants with programmable DNA nanobait.鈥� Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01287-x

A new test that 鈥榝ishes鈥� for multiple respiratory viruses at once using single strands of DNA as 鈥榖ait鈥�, and gives highly accurate results in under an hour, has been developed by Cambridge researchers.

Good diagnostics are the key to good treatments

Filip Bo拧kovi膰

Natalia Gdovskaia via Getty Images

Doctor examining a patient

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