Study reveals genetic link between childhood brain disorder and Parkinson's disease in adults

Image Credit: Dmitriy Kievskiy

Errors in a gene known to cause a serious neurodevelopmental condition in infants are also linked to the development of Parkinson’s disease in adolescence and adulthood, according to new research

The study, published in the Annals of Neurology, looked at a gene called EPG5. Errors in this gene are already known to cause Vici syndrome – a rare and severe inherited neurodevelopmental condition that presents early in life and affects multiple organ systems. Now researchers at King’s College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing have found that errors in the same gene are linked to changes in nerve cells that lead to more common age-related conditions like Parkinson’s disease and dementia.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Researchers discover of a new type of diabetes in babies

Photo Credit: Rene Terp

Advanced DNA sequencing technologies and a new model of stem cell research has enabled an international team to discover a new type of diabetes in babies.

The University of Exeter Medical School worked with Université Libre de Bruxelles (ULB) in Belgium and other partners to establish that mutations in the TMEM167A gene are responsible for a rare form of neonatal diabetes.

Some babies develop diabetes before the age of six months. In over 85 per cent of cases this is due to genetic mutation in their DNA. Research led by the University of Exeter found that in six children with additional neurological disorders such as epilepsy and microcephaly identified alterations in a single gene: TMEM167A.

To understand its role, ULB researcher Professor Miriam Cnop’s team used stem cells differentiated into pancreatic beta cells and gene-editing techniques (CRISPR). They found that when the TMEM167A gene is altered, insulin-producing cells can no longer fulfill their role. They then activate stress mechanisms that lead to their death.

Breast Cancer Polygenic Risk Score Associated with Outcomes after In Situ Breast Disease

Photo Credit: National Cancer Institute

Studying a person’s genetic makeup can predict if they will go on to develop invasive breast cancer after abnormal cells have been found in their breast tissue.

For the first time, researchers at King’s College London have shown the connection between a person’s genetic risk score and their risk of developing the disease after irregular cells have been detected.

The research, published in Cancer Epidemiology, Biomarkers & Prevention and funded by Breast Cancer Now, included over 2,000 women in the UK who had been tested for 313 genetic changes, known as a genetic risk score.

These patients had already been diagnosed with either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) – the most common types of abnormal cells found in breast tissue.

A genetic risk score estimates a person's inherited likelihood of developing a disease or trait by combining the influence of multiple common genetic variants.

Hidden genetic risk could delay diabetes diagnosis for Black and Asian men

 

Photo Credit: Barbara Olsen

A common but often undiagnosed genetic condition may be causing delays in type 2 diabetes diagnoses and increasing the risk of serious complications for thousands of Black and South Asian men in the UK – and potentially millions worldwide.

The new study is conducted by the University of Exeter, in collaboration with Queen Mary University of London (QMUL) and funded through a Wellcome Discovery Award. It has found around one in seven Black and one in 63 South Asian men in the UK carry a genetic variant known as G6PD deficiency. Men with G6PD deficiency are, on average, diagnosed with type 2 diabetes four years later than those without the gene variant. But despite this, fewer than one in 50 have been diagnosed with the condition

G6PD deficiency does not cause diabetes, but it makes the widely used HbA1c blood test – which diagnoses and monitors diabetes – appear artificially low. This can mislead doctors and patients, resulting in delayed diabetes diagnosis and treatment.

Early changes during brain development may hold the key to autism and schizophrenia

Photo Credit: Michal Jarmoluk

Researchers at the University of Exeter have created a detailed temporal map of chemical changes to DNA through development and aging of the human brain, offering new insights into how conditions such as autism and schizophrenia may arise.

The team studied epigenetic changes – chemical tags on our DNA that control how genes are switched on or off. These changes are crucial in regulating the expression of genes, guiding brain cells to develop and specialize correctly.

One important mechanism, called DNA methylation, was examined in nearly 1,000 donated human brains, spanning life from just six weeks after conception through to 108 years of age. The researchers focused on the cortex, a region of the brain involved in high-level functions such as thought, memory, perception, and behavior. Correct development of the cortex during early life is important to support healthy brain function after birth.

Decoding the selfish gene, from evolutionary cheaters to disease control

Malaysian stalk-eyed fly (Teleopsis dalmanni).
Photo Credit: Paul Richards

New research is shining a light on one of genetics’ enduring puzzles - how the workings of the so-called “selfish gene” could be harnessed to control harmful insect populations.

Scientists from the University of Sheffield have uncovered how to potentially control harmful insect populations by studying a "selfish gene" that manipulates inheritance

The new research focuses on meiotic drive, a process where a selfish gene gives itself a better chance of being passed on to the next generation, disrupting the normal 50/50 inheritance pattern

By studying the Malaysian stalk-eyed fly, researchers discovered that a selfish gene can damage rival sperm carrying a Y chromosome, leading to a population with far more females than males

Understanding this genetic mechanism could provide a new way to control insects that spread disease and cause food shortages by causing their populations to become unsustainably female-biased

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

Genetic research unlocks new ways to prevent and treat multiple long-term conditions

Image Credit: Scientific Frontline stock image

The largest study to date to analyze millions of both genetic and patient records on the long-term health conditions of later life has identified opportunities for new ways to prevent and treat multiple overlapping conditions.  

Currently, nine million people in the UK live with two or more long-term conditions at the same time – known as multimorbidity. Their treatment accounts for half of the NHS budget. 

Led by the University of Exeter Medical School and funded by the Medical Research Council and the National Institute for Health and Care Research, the GEMINI study looked at both genetics and clinical information from more than three million people in the UK and Spain.  

Published in eBioMedicine  research has identified genetic overlaps in 72 long-term health conditions associated with ageing, to identify where specific genes are linked to two or more conditions. With more than 2,500 combinations of conditions analyzed, the program aims to unlock cases where a drug or prevention strategies can prevent or delay the onset of multimorbidity. It also revealed genetic connections that explain why certain conditions may be more likely to co-occur in the same patient. 

Mutations in two gene pairs point to a promising drug target in 5 percent of adult cancers

Illustration Credit: Natalie Velez, Broad Communications

Scientists from the Cancer Dependency Map (DepMap) at the Broad Institute of MIT and Harvard and Columbia University have discovered that about 5 percent of adult cancers rely heavily on a gene called PELO to survive and that disabling the gene kills those cancer cells. These cancers have mutations in one of two genes, FOCAD or TCC37.

The finding, described in Nature, is a new synthetic lethality — a pair of genetic changes that together kill cancer cells. The researchers say that PELO is a promising target, and that genetic testing could identify cancer patients with FOCAD or TCC37 mutations who would benefit from new PELO-targeting drugs.

“These cancers are a huge unmet medical need, because we don’t have effective drugs for them,” said Francisca Vazquez, co-senior author on the study along with postdoctoral researcher Edmond Chan, now an assistant professor at Columbia University. Vazquez is also director of DepMap, which systematically probes cancer cell lines for genetic vulnerabilities. 

“Targeting synthetic lethalities is a good way to expand the repertoire of tumors we’re able to treat,” Vazquez said. “This new synthetic lethality we found shows how powerful the DepMap datasets can be.”

Patricia Borck, a DepMap research scientist in Broad’s Cancer Program, is first author on the study.

Cutting edge technology shows promise in tackling deadly brain tumors

Delivering advanced gene-editing tools directly to the tumor site can improve the body’s defense against glioblastoma
Image Credit: Gemini

A new study led by Khuloud Al Jamal, Professor of Drug Delivery & Nanomedicine, has found an innovative strategy to combat glioblastoma (GB), a fast-growing and aggressive type of brain tumor.

GB is a brain tumor originating in the brain or spinal cord. Despite advances in cancer treatment, it can remain resistant to therapies, including immune checkpoint (ICP) blockade therapies. ICP blockade works by targeting specific proteins on immune or tumor cells to prevent tumors from evading the immune system. While effective in other cancers, this approach has shown limited success in treating GB. The is due to complex interactions between immune cells and glioblastoma stem cells (GSCs), which suppress the immune response and reduce the effectiveness of these therapies.

In the study, published in Advanced Science, Professor Al Jamal and her team revealed how they have taken a novel approach to overcome this challenge by focusing on the mesenchymal subtype of GSCs, which is particularly aggressive and therapy resistant. The study employed lipid nanoparticles (LNPs) — tiny, fat-based carriers — to transport CRISPR RNAs, an advanced gene-editing tool, to GSC and immune cells in therapeutically relevant tumor models. 

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

A genome-wide atlas of cell morphology reveals gene functions

Human cells imaged using Cell Painting. Cell nuclei are shown in blue, actin filaments in yellow, the endoplasmic reticulum in magenta, golgi bodies in cyan, and mitochondria in green.
Image Credit: Maria Lozada, Neal Lab

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. But using microscopy to do this at scale can be challenging, particularly when studying thousands of genes at a time.

Now, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. 

PERISCOPE — which stands for perturbation effect readout in situ via single-cell optical phenotyping — combines two technologies developed by Broad scientists: Cell Painting, which can capture images and key measures of subcellular compartments at scale, and Optical Pooled Screening, which “barcodes” cells and uses CRISPR to systematically turn off individual genes to study their function in those cells. 

The new technique lets scientists study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. Generating data with this method is more than 10 times less expensive than comparable high-dimensional approaches such as high-throughput single-cell RNA sequencing and can be adapted to study a wide variety of cell types. In Nature Methods, the researchers applied PERISCOPE to execute three whole-genome CRISPR screens to create an open-source atlas of cell morphology.

Eight Psychiatric Disorders Share the Same Genetic Causes

Image Credit: Won Lab

Building off previous groundbreaking research, a new study identifies specific genetic variants that have significant impacts on brain development and are shared across eight different psychiatric disorders. Targeting these variants could pave the way for treatments that address multiple conditions at once.

Psychiatric disorders often overlap and can make diagnosis difficult. Depression and anxiety, for example, can coexist and share symptoms. Schizophrenia and anorexia nervosa. Autism and attention deficit/hyperactivity disorder, too. But, why?

Life experiences, environment, and genetics can all influence psychiatric disorders, but much of it comes down to variations in our genetics. Over the past few years, scientists in the field of psychiatric genetics have found that there are common genetic threads that may be linking and causing coexisting psychiatric disorders.

In 2019, researchers at the Psychiatric Genomics Consortium, Harvard University, and the UNC School of Medicine identified 136 “hot spots” within the genome that are associated with eight psychiatric disorders. Among them, 109 hot spots were shared among multiple disorders, or “pleiotropic”. However, it was not clear at the time how genetic variations within these hot spots differed from those that only have roles in only one disorder.

Gene editing extends lifespan in mouse model of prion disease

Broad Communications Eric Minikel and Sonia Vallabh run a lab with a singular focus: preventing and treating prion disease within their lifetime.
Photo Credit: Maria Nemchuk

Researchers at the Broad Institute of MIT and Harvard have developed a gene-editing treatment for prion disease that extends lifespan by about 50 percent in a mouse model of the fatal neurodegenerative condition. The treatment, which uses base editing to make a single-letter change in DNA, reduced levels of the disease-causing prion protein in the brain by as much as 60 percent. 

There is currently no cure for prion disease, and the new approach could be an important step towards treatments that prevent the disease or slow its progression in patients who have already developed symptoms. A base-editing approach could also likely be a one-time treatment for all prion disease patients regardless of the genetic mutation causing their disease. 

The work, led by Broad senior group leaders Sonia Vallabh and Eric Minikel, as well as Broad core institute member David Liu, is the first demonstration that lowering levels of the prion protein improves lifespan in animals that have been infected with a human version of the protein. The findings appear in Nature Medicine.

Chornobyl Dogs’ Genetic Differences Not Due to Mutation

Photo Credit: Norman Kleiman

Radiation-induced mutation is unlikely to have induced genetic differences between dog populations in Chornobyl City and the nearby Chornobyl Nuclear Power Plant (NPP), according to a new study in PLOS ONE from North Carolina State University and Columbia University Mailman School of Public Health. The study has implications for understanding the effects of environmental contamination on populations over time.

“We have been working with two dog populations that, while separated by just 16 kilometers, or about 10 miles, are genetically distinct,” says Matthew Breen, Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics at NC State. “We are trying to determine if low-level exposure over many years to environmental toxins such as radiation, lead, etcetera, could explain some of those differences.” Breen is the corresponding author of the study.

Previously, the team had analyzed genetic variants distributed across the genome and identified 391 outlier regions in the dogs that differed between the two populations. Some of these regions contained genes associated specifically with repair of DNA damage. In this new study, the researchers conducted a deeper dive into the genomes of the dogs to detect evidence of mutations that may have accumulated over time.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

Single genomic test could speed up diagnoses for rare genetic diseases

Image Credit: Sinousxl

A new approach to analyzing exome sequencing data reliably detects large-scale genetic changes and could reduce the number of genetic tests a child might need.

A single genetic test could potentially replace the current two-step approach to diagnosing rare developmental disorders in children, enabling earlier diagnoses for families and saving the NHS vital resources.

Researchers from the University of Exeter, along with collaborators at the Wellcome Sanger Institute, and the University of Cambridge, reassessed genetic data from nearly 10,000 families from the Deciphering Developmental Disorders study.

In a new study, recently published in Genetics in Medicine, they show for the first time that using exome sequencing – which reads only protein-coding DNA – is as accurate, if not better, than standard microarrays at identifying disease-causing structural genetic variations.

Its adoption offers hope for faster and more accurate diagnoses of rare genetic diseases. It could also deliver substantial cost savings for the NHS, though more training is needed for specialists to generate and analyze the data, say researchers.

Cystic fibrosis: why infections persist despite therapy

The anchor points present on the surface of the airways in cystic fibrosis (left image, in red) decrease when the balance between the two cell signaling pathways is restored (right image).
Image Credit: Marc Chanson et al, 2024

Cystic fibrosis is a genetic disease that causes serious and sometimes fatal respiratory and digestive disorders. A new treatment, available since 2020, improves lung function and quality of life. However, it does not always eradicate the bacteria responsible for respiratory infections. By studying 3D models of human lung cells, scientists at the University of Geneva (UNIGE) discovered that this drug does not prevent the development on the surface of the respiratory tract of ''docking stations'' to which bacteria attach themselves to infect the body. These docking stations result from a disruption in the signals involved in cell development in the respiratory system. By combining the current treatment with other molecules, it may be possible to restore cell balance and thus better prevent bacterial infections. These results are published in the American Journal of Respiratory Cell and Molecular Biology.

Cystic fibrosis is the most common genetic disease. Each year, it affects one in every 3,300 newborns in Switzerland. Mutations in the gene responsible for the CFTR protein cause the secretion of excessively thick mucus, which obstructs the airways. Although a triple therapy, available in Switzerland since 2020, has improved the quality of life of people with cystic fibrosis, it is not suitable for all those affected and does not always prove effective.

New sunflower family tree reveals multiple origins of flower symmetry

A new sunflower family tree reveals that flower symmetry evolved multiple times independently. Chrysanthemum lavandulifolium, on the upper left, and Artemisia annua, upper right, are closely related species from the same tribe; the former has bilaterally symmetric flowers — the rays — and the latter does not. Rudbeckia hirta, lower left, from the sunflower tribe has bilaterally symmetric flowers, and Eupatorium chinense, lower right, from the Eupatorieae tribe does not; these two tribes are closely related groups. A sunflower, center, shows flowers with bilateral symmetry — the large petal-like flowers in the outer row — and without bilateral symmetry — the small flowers in the inner rows.
Photo Credits: Guojin Zhang, Ma laboratory / Pennsylvania State University
(CC BY-NC-ND 4.0 DEED)

The sunflower family tree revealed that flower symmetry evolved multiple times independently, a process called convergent evolution, among the members of this large plant family, according to a new analysis. The research team, led by a Penn State biologist, resolved more of the finer branches of the family tree, providing insight into how the sunflower family — which includes asters, daisies and food crops like lettuce and artichoke — evolved.

A paper describing the analysis and findings, which researchers said may help identify useful traits to selectively breed plants with more desirable characteristics is available online and will be published in an upcoming print edition of the journal Plant Communications.

“Convergent evolution describes the independent evolution of what appears to be the same trait in different species, like wings in birds and bats,” said Hong Ma, Huck Chair in Plant Reproductive Development and Evolution, professor of biology in the Eberly College of Science at Penn State and the leader of the research team. “This can make it difficult to determine how closely related two species are by comparing their traits, so having a detailed family tree based on DNA sequence is crucial to understanding how and when these traits evolved.”