JAX research roundup: hidden DNA, genome editing and more

Hidden DNA features key to disease and evolution revealed with globally diverse genomes

By decoding DNA segments once thought too complex to analyze, an international team of scientists has set a new gold standard for genome sequencing that could propel the field toward a more complete and inclusive vision of human biology. The work uncovered once-elusive details of DNA by producing complete sequences from diverse ancestries, revealing variations that affect digestion, immune function and muscle control. The findings could help explain why certain diseases strike some populations harder than others and ensure that future research benefits all people — not just those historically overrepresented.

Read the full story

Researchers harness AI to discover “invisible” chronic fatigue biomarkers

What if routine lab tests could tell doctors if you had a hard-to-diagnose disease? Scientists and clinicians have revealed how myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disrupts the body’s microbiome, immune system, and metabolism. Potentially relevant for long COVID due to its similarity to chronic fatigue syndrome, the insights come from patient data analyzed with a new AI platform designed to rapidly detect disease biomarkers from stool, blood, and other routine lab tests with 90% accuracy. The tool also achieved nearly 80% accuracy in external data sets. This suggests ME/CFS causes identifiable biological dysregulation that has long eluded detection in medicine. 

Read the full story

Genome editing corrected rare brain mutations in mice. Could it help fight neurological diseases?

Scientists corrected gene mutations in mice causing an ultra-rare childhood disease by editing DNA directly in the brain, a major feat that could accelerate treatments for neurological disease patients. In tests that also included patient-derived cells, the technique fixed mutations causing alternating hemiplegia in childhood (AHC), reducing symptoms and extending the survival of mice with AHC who were otherwise at risk of sudden death. Led by JAX’s Rare Disease Translational Center, the Broad Institute, and the nonprofit RARE Hope, the study offers a glimpse into how personalized gene editing could scale to help patients with other brain diseases.

Read the full story

Why patients with mitochondrial disease are more susceptible to infections

Recent research revealed how dysfunctional mitochondria put the immune system on overdrive, an excessive response that likely makes patients with rare mitochondrial diseases highly vulnerable to severe infections. The scientists focused on a rare and progressive mitochondrial disorder called polymerase gamma disease (PolG). Using mice with the same genetic mutation found in human patients, scientists showed that inflammation and tissue damage combine to make infections far more deadly. Understanding this mitochondria-inflammation link could lead to better treatments across multiple diseases, as mitochondrial damage is also linked to neurodegenerative diseases, severe COVID-19 and other conditions that affect millions worldwide.

Read the full story

Supercharged mitochondria boosts aging-related blood disorders

With age, blood stem cells can accumulate mutations that make them multiply faster than normal, raising the risk for serious diseases. Recent research reveals how a common age-related mutation in the gene Dnmt3a powers this process. The mutation supercharges the cells’ mitochondria, allowing stem cells to multiply more rapidly than normal ones. In middle-aged mice, the mutated cells had twice the energy output of normal ones, helping them take over and drive a condition called clonal hematopoiesis linked to heart disease, blood cancer, and other illnesses. The findings could point to new ways to stop this cellular process before it leads to disease.

Read the full story