- Revealing how an ancient genetic invader inhabits our DNA Medical Xpress
- Dark Genome Discovery: Researchers Reveal “Ancient Genetic Parasite” Implicated in Human Diseases SciTechDaily
- Research Spotlight: Structural Analysis and Inhibition of Human LINE-1 ORF2 Protein Reveals Novel Adaptations and Functions. Massachusetts General Hospital
- Revealing how an ancient genetic invader inhabits our DNA – News The Rockefeller University
- ROME Publishes Landmark Nature Paper Revealing First High-Resolution Structure of LINE-1 Reverse Transcriptase (RT) for Drug Discovery Manchestertimes
Tag Archives: genetic
DNA Breakthrough – How Genetic Shedding Unveils Species Secrets – SciTechDaily
- DNA Breakthrough – How Genetic Shedding Unveils Species Secrets SciTechDaily
- eDNA data collection in The Ocean Race could provide crucial insights on ocean biodiversity Sail World
- Racing boat collects eDNA samples on a round-the-world sailing competition Earth.com
- ‘Environmental DNA’ Data Collection in The Ocean Race Could Provide Crucial Insights on Ocean Biodiversity Afloat
- Environmental DNA detects biodiversity and ecological features of phytoplankton communities in Mediterranean transitional waters | Scientific Reports Nature.com
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Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe | Communications Biology – Nature.com
- Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe | Communications Biology Nature.com
- Largest-ever genetic family tree reconstructed for Neolithic people in France using ancient DNA Livescience.com
- Stone Age Secrets Unveiled: A DNA Dive Into Europe’s Genetic and Cultural Past SciTechDaily
- New research links early Europeans’ cultural and genetic development over several thousand years Phys.org
- DNA Analysis Redirects the Cradle of Indo-Europeans, Sheds Light on Proto-Greeks Greek Reporter
- View Full Coverage on Google News
Dual CRISPR Gene Editing Strategy Cures Animals of HIV-1 – Genetic Engineering & Biotechnology News
- Dual CRISPR Gene Editing Strategy Cures Animals of HIV-1 Genetic Engineering & Biotechnology News
- UNMC, Temple research increases chances of eliminating HIV infection University of Nebraska Medical Center
- Dual CRISPR therapy plus long-acting ART eliminates HIV in mice FierceBiotech
- CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice | Proceedings of the National Academy of Sciences pnas.org
- Chances of eliminating HIV infection increased by novel dual gene-editing approach Medical Xpress
- View Full Coverage on Google News
FDA finally approves Reata’s rare genetic disease drug – Endpoints News
- FDA finally approves Reata’s rare genetic disease drug Endpoints News
- FDA Widens Path for Rare-Disease Treatments With New Approval The Wall Street Journal
- RETA Stock Skyrockets As FDA Approves Reata Phama’s Neurological Drug | Investor’s Business Daily Investor’s Business Daily
- Reata Pharmaceuticals Announces FDA Approval of SKYCLARYS™ (Omavaloxolone), the First and Only Drug Indicated for Patients with Friedreich’s Ataxia Business Wire
- FDA approves Reata’s treatment for rare neurological disease STAT
- View Full Coverage on Google News
Genetic Mutation Makes New Subvariant Extra Contagious – Rolling Stone
There’s a new, more contagious form of the novel-coronavirus. It’s got a greater ability to evade our antibodies. And it’s spreading easier than ever.
You’ve read these words before, and you’ll almost certainly read them again as the Covid pandemic grinds into its fourth calendar year. But pay attention, because there’s something new about XBB.1.5, also known as Kraken, the latest Omicron subvariant that’s quickly becoming the dominant form of SARS-CoV-2 across much of the world. XBB.1.5 evolved after a couple of big genetic twists and turns.
The virus still has the potential to surprise us. And that can mean only one thing: “SARS-CoV-2 seems like it’s going to be with us for a long time,” says Matthew Frieman, a University of Maryland School of Medicine immunologist and microbiologist.
Kraken features a key mutation that geneticists call “F486P.” It’s a seemingly small change on the spike protein, the part of the virus that helps it to grab onto and infect our cells. F486P works by boosting the spike’s ability to “bind” to one particular part of our cells called the ACE2 receptor. That small change has enormous implications. F486P allows XBB.1.5 to retain all the most dangerous qualities of its parent subvariants, while also adding a new quality: extreme transmissibility.
Basically, F486P makes XBB.1.5 really, really contagious — much more contagious than its immediate predecessors. But it also inherited from these same predecessors an alarming potential to evade our antibodies. “Due to the F486P spike mutation, XBB.1.5 exhibits a substantially higher viral receptor-binding affinity … while it retains similar antibody-evasion [properties],” says Lihong Liu, a Columbia University Covid Covid researcher. In short, XBB.1.5 is the first subvariant in its immediate family to be both more immune-evasive and more contagious.
The appearance of the F486P mutation is a reminder that, even as many people get on with their lives, the pandemic isn’t nearly over. The virus keeps finding ways to spread faster while also increasingly sneaking past all those antibodies we’ve built up from vaccines, boosters, and past infection.
XBB.1.5 first showed up in viral samples in the northeast United States back in October. Two months later, it’s present in nearly 30 countries and, according to the latest projection from the U.S. Centers for Disease Control and Prevention, could already be the dominant form of Covid in the United States. Not coincidentally, there’s been a surge in serious Covid cases in the Northeast U.S., XBB.1.5’s birthplace and the region where it’s thickest in the air.
We’ve been through this sort of thing before, of course. Some new subvariant evolves, becomes dominant and drives a surge in cases. But by now, most people in most countries have a healthy mix of Covid antibodies from vaccines, past infection, or both. So while infection rates rise and fall to the rhythm of viral evolution, hospitalizations and deaths have been trending downward in most of the world for many months now.
There’s no reason to expect XBB.1.5 will significantly alter this dynamic. For all its new genetic wrinkles, it’s still Omicron. And between vaccines, boosters, and immunity from past infection, we’ve got lots of ways to protect against that particular variant and its offspring.
If there’s a big exception, it’s China, where three years of lockdown finally began lifting in early December following widespread public protest. Now the Chinese health system is buckling under the country’s first big, nationwide Covid outbreak. Notably, XBB.1.5 hasn’t shown up in China. Yet.
Most of the world is in a pretty good position to struggle through XBB.1.5. China isn’t. For many hundreds of millions of Chinese with weaker immunity, COVID’s evolutionary twists and turns are pretty ominous.
It started with BA.2 and BA.2.75, two of the early Omicron subvariants that were dominant in many countries last spring and summer, respectively. At some point, someone — or several someones — who had recovered from BA.2 caught BA.2.75, or vice versa. The two forms of the virus combined in those hosts, producing the “recombinant” XBB, which later evolved into XBB.1 and then XBB.1.5.
Peter Hotez, an expert in vaccine development at Baylor College, describes these recombinants as “Scrabble” variants. “Because they tend to use high-value Scrabble letters like X, B and Q.” What they all have in common is that they’re “receptor-binding domain escape variants,” Hotez says.
In plain English, they’ve got sticky spike proteins and they’re really good at dodging our antibodies, especially the antibodies we get from vaccines. “In my understanding, XBB.1, the parent of XBB.1.5 is almost completely resistant to vaccine-induced humoral immunity,” says Kei Sato, a University of Tokyo virologist.
But XBB.1.5 is even stickier and more evasive. And it’s all because of the F486P mutation. The original XBB and its immediate offspring XBB.1 included F486S rather than F486P. F486S altered the spike protein, but didn’t make the spike protein any stickier and thus more transmissible.
With F486P, XBB and XBB.1 achieved greater immune-evasion without also adding greater transmissibility. Then XBB.1.5 came around and bucked that comforting trend. The mutation upgrade, from F486S to F486P, made the spike protein stickier and the virus more transmissible.
For most of us, this genetic innovation is most worrying for the trend that it signals. There was some speculation as early 2021 — just six months or so into the pandemic — that SARS-CoV-2 would run out of genetic space, so to speak, and stop mutating in significant ways.
That hasn’t happened. “There seems to be still more mutational space in the genome,” Frieman says. XBB.1.5 is proof that the virus can still change, still get more contagious and more evasive. That it can, after all this time, still surprise us.
Support From Others in Stressful Times Can Ease Impact of Genetic Depression Risk
Summary: Social support during stressful times helps reduce the risk of those with genetic predispositions to depression from developing symptoms.
Source: University of Michigan
Reaching out to support a person when they’re under stress is always a good idea. But a new study suggests that support could be especially important for someone whose genetic makeup makes them more likely to develop depression.
The study shows the importance of social support in buffering the risk of developing depression symptoms in general, using data from two very different groups of people under stress: new doctors in the most intense year of training, and older adults whose spouses recently died.
But the largest effect was seen in those who had the most genetic variation that raised the risk of depression.
The paper uses a measure of genetic risk called a polygenic risk score, which is based on decades of research about what tiny variations in specific genes are linked to depression risk.
Compared to individuals in the study who had low depression polygenic risk scores, the doctors and widows with higher risk scores had higher rates of depression after they lost social support, but also had lower rates of depression when they gained social support during stressful times.
The study, published in the American Journal of Psychiatry by a University of Michigan team, suggests that more could be done to target social support to those who can most benefit.
Genes, stress and social connection
“Our data show wide variability in the level of social support individuals received during these stressful times, and how it changed over time,” said first author Jennifer Cleary, M.S., a psychology doctoral student at U-M who is doing her research with senior author Srijan Sen, M.D., Ph.D., of the U-M Medical School.
“We hope these findings, which incorporate genetic risk scores as well as measures of social support and depressive symptoms, illuminate the gene-environment interactions and specifically the importance of social connection in depression risk.”
Sen, who is the director of the Eisenberg Family Depression Center and a professor of psychiatry and neuroscience, adds that even as genetic research reveals more of the DNA variation related to depression vulnerability, learning how that variation leads to depression is crucial.
“Further understanding the different genetic profiles associated with sensitivity to loss of social support, insufficient sleep, excessive work stress and other risk factors could help us develop personalized guidance for depression prevention,” he said.
“In the meantime, these findings reaffirm how important social connections, social support and individual sensitivity to the social environment are as factors in well-being and preventing depression.”
Different populations, similar patterns
The new study used data from two long-term studies that both capture genetic, mood, environment and other data from populations of participating individuals.
One is the Intern Health Study, which enrolls first-year medical residents (also called interns) around the United States and beyond, and which Sen directs.
The other is the Health and Retirement Study, based at the U-M Institute for Social Research.
The data for the new paper came from 1,011 interns training at hospitals across the country, nearly half of whom were female, and from 435 recently widowed individuals, 71% of them women, who had data available from surveys conducted before and after their spouses died.
In the interns, as Sen and his team have shown in previous work, depressive symptoms increased dramatically (126%) during the stressful year of training that includes long and irregular work hours—often in environments far from friends and family.
In the widows and widowers, depressive symptoms increased 34% over their pre-widowhood scores. This correlates with past research showing loss of a spouse can be one of the biggest stressors in a person’s life, Cleary said.
A crossover effect
Then, the researchers factored together the depression symptom findings with each person’s polygenic risk score for depression, and their individual responses to questions about connections with friends, family and other social supporters.
Most of the interns lost social support from their pre-internship days—which fits well with the common experience of leaving the place where they attended medical school and going to a new environment where they may not know anyone.
Interns who had the highest polygenic risk scores and also lost social support had the highest scores on measures of depression symptoms later in the stressful intern year.
Those with the same high level of genetic risk who gained social support, though, had much lower depressive symptoms. In fact, it was lower than even their peers with low genetic risk, no matter what happened to their social support. The researchers call this a “crossover effect.”
Unlike the interns, some widowed individuals reported an increase in social support after the loss of their spouse, potentially as friends and family reached out to offer help or just a listening ear.
But the crossover effect was visible in them, too. Widows with high genetic risk for depression who gained social support showed a much smaller increase in depressive symptoms than their peers with similar genetic risk who lost social support after losing a spouse.
There were also some widows who lost social support or didn’t experience a change in support, and whose depressive symptoms didn’t change. Cleary notes that in future work, it will be important to look at this group’s history in light of any caregiving they may have done for a spouse with a long-term illness.
See also
The team also hopes that other researchers will study this same interaction of genetic risk, stress and social support in other populations.
In the meantime, Cleary and Sen say, the message for anyone going through stressful times, or watching a friend or relative go through stressful times, is to reach out and maintain or strengthen social connections.
Doing so can have benefits both for the person under stress, and the person reaching out to them, they note.
Reducing the level of ongoing stress that the person is facing, whether it’s at work, school, after a personal loss or in family situations can be critical.
And even though the study did not examine the role of professional mental health help, individual and group therapy is an important option for those who have developed depression or other mental health concerns.
About this genetics and depression research news
Author: Press Office
Source: University of Michigan
Contact: Press Office – University of Michigan
Image: The image is in the public domain
Original Research: Closed access.
“Polygenic Risk and Social Support in Predicting Depression Under Stress” by Jennifer L. Cleary et al. American Journal of Psychiatry
Abstract
Polygenic Risk and Social Support in Predicting Depression Under Stress
Objective:
Despite substantial progress in identifying genomic variation associated with major depression, the mechanisms by which genomic and environmental factors jointly influence depression risk remain unclear. Genomically conferred sensitivity to the social environment may be one mechanism linking genomic variation and depressive symptoms. The authors assessed whether social support affects the likelihood of depression development differently across the spectrum of genomic risk in two samples that experienced substantial life stress: 1,011 first-year training physicians (interns) in the Intern Health Study (IHS) and 435 recently widowed Health and Retirement Study (HRS) participants.
Methods:
Participants’ depressive symptoms and social support were assessed with questionnaires that were administered before and after the life stressor. Polygenic risk scores (PRSs) for major depressive disorder were calculated for both samples.
Results:
Depressive symptom scores increased by 126% after the start of internship in the IHS sample and by 34% after widowing in the HRS sample. There was an interaction between depression PRS and change in social support in the prediction of depressive symptoms in both the IHS sample (incidence rate ratio [IRR]=0.96, 95% CI=0.93, 0.98) and the HRS sample (IRR=0.78, 95% CI=0.66, 0.92), with higher depression PRS associated with greater sensitivity to changes in social support. Johnson-Neyman intervals indicated a crossover effect, with losses and gains in social support moderating the effect of PRS on depressive symptoms. (Johnson-Neyman interval in the IHS sample, −0.02, 0.71; in the HRS sample, −0.49, 1.92).
Conclusions:
The study findings suggest that individuals with high genomic risk for developing increased depressive symptoms under adverse social conditions also benefit more from nurturing social environments.
Head Trauma and PTSD May Increase Genetic Variant’s Impact on Alzheimer’s Risk
Summary: The risk of developing Alzheimer’s disease and dementia-related symptoms is higher in those with TBI and PTSD who carry the APOE E4 gene.
Source: Veterans Affairs Research Communications
In a study of Veterans led by Dr. Mark Logue, a statistician in the National Center for PTSD at the VA Boston Healthcare System, researchers concluded that PTSD, TBI, and the ε4 variant of the APOE gene show strong associations with Alzheimer’s disease and related dementias (ADRD).
The medical community has never researched the simultaneous impact of post-traumatic stress disorder (PTSD), traumatic brain injury (TBI) and genetic risk factors in a large cohort until now. They first found a greater percentage of ADRD in Veterans with PTSD and in those with TBI, relative to those without, as well as higher rates of ADRD in Veterans who had inherited the ε4 variant. Logue and his team then looked for interactions between the ε4 variant, PTSD, and TBI using a mathematical model.
The study found an increase in risk due to PTSD and TBI in Veterans of European ancestry who inherited the ε4 variant. In Veterans of African ancestry, the impact of PTSD didn’t vary as a function of ε4, but the TBI effect and interaction with ε4 was even stronger. Other studies have suggested that ε4 may magnify the effects of a head injury and/or combat-related stress.
“These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles,” Logue and his colleagues wrote. “PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.”
Capitalizing on VA’s Million Veteran Program
The researchers carried out the study by accessing data from VA’s Million Veteran Program (MVP), one of the world’s largest databases of health and genetic information. MVP is aimed at learning how genes, lifestyle, and military exposures affect health and illness, with more than 900,000 Veterans enrolled in its climb to 1 million and beyond.
With more than 40% of the Veteran population above the age of 75, the number of former Service Members at risk for Alzheimer’s and other forms of dementia is rising. While large cohort studies have shown that PTSD and TBI increase the risk of dementia in Veterans, Logue and his colleagues investigated further by studying these risk factors along with the APOE ε4 variant. Most people don’t inherit that variant, but those who do inherit it from one parent (one copy) or both of their parents (two copies).
“Research has shown that if you inherit one copy of ε4, you’re at increased risk of Alzheimer’s disease,” he said, “and if you inherit two copies, you are at much higher risk.”
The number of ε4 variants a person inherits is fixed at birth, but their impact differs with age, according to Logue, who is also an Army Veteran and an associate professor at Boston University.
“The risk of Alzheimer’s disease increases with age for all of the APOE genotypes,” he said. “But when compared to people with two copies of the common variant, the difference in risk for those with a copy of ε4 appears to peak somewhere between age 65 and 70 and then decrease after that. Again, that doesn’t mean that your chances of Alzheimer’s decrease after that, just that the difference between the risk for those with and without ε4 diminishes.”
The study showed that the risk associated with PTSD and head injury was larger for ε4 carriers. Their model led the researchers to expect that for 80-year-old Veterans of European ancestry who didn’t inherit the ε4 variant, the percentage of ADRD would be 6% greater for those with PTSD compared to those without. But for 80-year-old Veterans of European ancestry who inherited two copies of ε4, the percentage of ADRD would be 11% higher for those with PTSD than those without.
Clear link between PTSD, TBI on dementia risk a surprise
Logue was most surprised to see such clear evidence of a link between PTSD and head trauma on dementia risk.
“I’ve worked in Alzheimer’s disease genetics for over a decade now, and I was used to seeing a clear impact of APOE ε4 on Alzheimer’s risk,” he says. “However, in this cohort, the effects of PTSD and head injury were just as clear and looked similar to the effect of inheriting ε4 from one of your parents.”
Next, Logue and his colleagues would like to use MVP data to research other risk factors that are relevant to Veterans, with the goal of learning how they may interact with Alzheimer’s risk variants. They are also looking to do genome-wide association scans to try to find new Alzheimer’s and dementia risk variants. The most recent large-scale genome-wide association study of Alzheimer’s identified some 80 variants linked to the risk of Alzheimer’s, Logue said, noting that those variants were rare or had a much smaller impact than ε4.
MVP data can be used to boost power for this type of study, he added, but PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and conducting accurate ADRD risk assessments.
“We know that genes play a large role in Alzheimer’s risk, but they don’t tell the whole story,” Logue explained.
“Right now, no genetic test can tell you if you’re certain to develop Alzheimer’s disease. Tests can only give an estimate of your likelihood of developing Alzheimer’s that may be higher or lower than average. Our study shows that these estimates will be more accurate if they incorporate more than just age and genetics.
See also
“In Veterans, a history of head injuries and PTSD can also make a large difference in dementia risk, so using that information will allow for more accurate measurement of the chances of developing dementia.”
About this neurology research news
Author: Mike Richman
Source: Veterans Affairs Research Communications
Contact: Mike Richman – Veterans Affairs Research Communications
Image: The image is in the public domain
Original Research: Open access.
“Alzheimer’s disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury” by Mark W. Logue et al et al. Alzheimer’s & Dementia
Abstract
Alzheimer’s disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury
Introduction
Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer risk for Alzheimer’s disease and related dementias (ADRD).
Methods
This study from the Million Veteran Program (MVP) evaluated the impact of apolipoprotein E (APOE) ε4, PTSD, and TBI on ADRD prevalence in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; n = 1443 ADRD cases, 16,191 controls). Additive-scale interactions were estimated using the relative excess risk due to interaction (RERI) statistic.
Results
PTSD, TBI, and APOE ε4 showed strong main-effect associations with ADRD. RERI analysis revealed significant additive APOE ε4 interactions with PTSD and TBI in the EA cohort and TBI in the AA cohort. These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles.
Discussion
PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.
We’ve Discovered A Subtle Genetic Imbalance That May Drive Aging : ScienceAlert
Scientists have found an extremely subtle twist in the genetics of aging cells, one that seems to make them increasingly less functional as time goes on.
Researchers from Northwestern University have revealed animals like mice, rats, killifish, and even humans show a gradual imbalance of long and short genes in virtually every cell in their body as they age.
The discovery suggests there aren’t specific genes that control the aging process. Instead, old age seems to be governed by systems-level changes with complex effects. And this can impact thousands of different genes and their respective proteins.
For an individual gene, however, the changes are so tiny as to be insignificant. That’s probably why they’ve slipped past our notice until now.
“We have been primarily focusing on a small number of genes, thinking that a few genes would explain disease,” says Northwestern University data scientist Luís Amaral.
“So, maybe we were not focused on the right thing before. Now that we have this new understanding, it’s like having a new instrument. It’s like Galileo with a telescope, looking at space. Looking at gene activity through this new lens will enable us to see biological phenomena differently.”
Normally, in an individual cell or a group of cells, a code represented in DNA is translated into RNA, becoming a collection of free-floating instructions known as a transcriptome.
This mobile library of genetic recipes is what the cell uses to create its parts and carry out its various functions. Its contents also seem to change with age.
In a healthy, young animal, the activity of short and long genes is balanced across a transcriptome, and this balance is carefully monitored and maintained. But as an individual grows older, short genes become more of a dominant trend.
In several different types of animals, in fact, shorter transcriptomes were found to proliferate with age.
“The changes in the activity of genes are very, very small, and these small changes involve thousands of genes,” explains developmental biologist Thomas Stoeger.
“We found this change was consistent across different tissues and in different animals. We found it almost everywhere. I find it very elegant that a single, relatively concise principle seems to account for nearly all of the changes in activity of genes that happen in animals as they age.”
Like the process of aging itself, the transition to smaller transcriptomes starts early and is gradual.
In rats, tissue samples taken at 4 months of age had a relatively longer median length of genes than those taken at 9 months of age.
The transcriptome changes found in killifish from the age of 5 weeks to 39 weeks were similar.
To test the pattern in humans, researchers turned to data from the Genotype-Tissue Expression (GTEx) project, which publicly provides genetic information collected from almost 1,000 deceased individuals.
Among humans, transcriptome length was once again found to be predictive of older age, becoming significant in the 50 to 69 age group.
Compared to the younger age group of 30 to 49, the older group showed longer transcripts that were less likely to ‘fold’ or become functionally active compared to shorter ones.
“The result for humans is very strong because we have more samples for humans than for other animals,” says Amaral.
“It was also interesting because all the mice we studied are genetically identical, the same gender, and raised in the same laboratory conditions, but the humans are all different. They all died from different causes and at different ages. We analyzed samples from men and women separately and found the same pattern.”
Not yet satisfied with their results, researchers at Northwestern next investigated the effect of several anti-aging interventions on the length of transcriptomes. The majority of interventions favored long transcripts, despite their differing impacts on the body.
The authors conclude that aging cannot be boiled down to a single origin of transcriptome imbalance.
Instead, they argue that “multiple environmental and internal conditions” probably lead to short genes becoming more active in the body.
“Spurred by our findings on anti-aging interventions, we believe that understanding the direction of causality between other age-dependent cellular and transcriptomic changes and length-associated transcriptome imbalance could open novel research directions for anti-aging interventions,” the authors conclude.
The study was published in Nature Aging.
Genome sequencing trial to test benefits of identifying genetic diseases at birth | Genetics
Genomics England is to test whether sequencing babies’ genomes at birth could help speed up the diagnosis of about 200 rare genetic diseases, and ensure faster access to treatment.
The study, which will sequence the genomes of 100,000 babies over the next two years, will explore the cost-effectiveness of the approach, as well as how willing new parents are to accept it.
Although researchers will only search babies’ genomes for genetic conditions that surface during early childhood, and for which an effective treatment already exists, their sequences will be held on file. This could open the door to further tests that could identify untreatable adult onset conditions, or other genetically determined traits, in the future.
“One challenging thing with newborn genomes is that they will potentially accompany people from cradle to grave,” said Sarah Norcross, director of the Progress Educational Trust (PET), an independent charity that improves choices for people affected by infertility and genetic conditions.
Ensuring the privacy of this data is therefore essential. “People must be able to trust that any data collected will only be used in the agreed way, and for the stated purpose,” Norcross said.
Each year, approximately 3,000 children are born in the UK with a treatable rare condition that could be detected using genome sequencing. Although newborn babies are currently offered a heel-prick test to screen their blood for signs of nine rare but serious conditions, such as sickle cell disease and cystic fibrosis, whole genome sequencing could enable hundreds more such conditions to be diagnosed at birth.
Currently, such diseases are usually only diagnosed once a child develops symptoms, often after months or years of tests. One such condition is biotinidase deficiency, an inherited disorder in which the body is unable to recycle the vitamin biotin. Affected children may experience seizures and delays in reaching developmental milestones, and have problems with vision or hearing, but early diagnosis and treatment with biotin supplements can prevent this deterioration and keep them healthy.
Dr Richard Scott, chief medical officer at Genomics England, said: “At the moment, the average time to diagnosis in a rare disease is about five years. This can be an extraordinary ordeal for families, and it also puts pressure on the health system. The question this programme is responding to is: ‘is there a way that we can get ahead of this?’”
The study aims to recruit 100,000 newborn children to undergo voluntary whole genome sequencing over the next two years, to assess the feasibility and effectiveness of the technology – including whether it could save the NHS money by preventing serious illness.
It will also explore how researchers might access an anonymised version of this database to study people as they grow older, and whether a person’s genome might be used throughout their lives to inform future healthcare decisions. For instance, if someone develops cancer when they are older, there may be an opportunity to use their stored genetic information to help diagnose and treat them.
According to research commissioned by PET earlier this year, 57% of the UK public would support the storage of genetic data in a national database, provided it were only accessible to the sequenced individual and healthcare professionals involved in their care. Only 12% of people opposed this.
Of greater concern would be the storage of a person’s genetic data for use by government authorities including the police, with the person being identifiable to those authorities. This was supported by 40% of people, and opposed by 25%. Norcross said that while Genomics England has good safeguards in place for providing research access to genomic data, “this risk can never be eliminated completely”.
Scott stressed that the purpose of the trial was to explore whether the potential benefits of newborn sequencing stack up, and engage in a genuine national debate about whether the technology is something people feel comfortable with. “The bottom line here is about us taking a cautious approach, and developing a view jointly nationally about what the right approach is, and what the right safeguards are,” he said.
Others raised concerns about the potential for false or uncertain results. Frances Flinter, emeritus professor of clinical genetics at Guy’s & St Thomas NHS foundation trust, and a member of the Nuffield council on bioethics, said: “Using whole genome sequencing to screen newborn babies is a step into the unknown. Getting the balance of benefit and harm right will be crucial. The potential benefits are early diagnosis and treatment for more babies with genetic conditions. The potential harms are false or uncertain results, unnecessary anxiety for parents, and a lack of good follow-up care for babies with a positive screening result.
“We must not race to use this technology before both the science and ethics are ready. This research programme could provide new and important evidence on both. We just hope the question of whether we should be doing this at all is still open.”