New research is transforming our understanding of human biology and raising the bar for precision medicine.

An international team of scientists has successfully decoded some of the most complex and previously overlooked regions of the human genome by analyzing complete sequences from 65 individuals representing diverse ancestries. Published in Nature and co-led by The Jackson Laboratory (JAX) and UConn Health, the study uncovers hidden DNA variations that affect key biological functions such as digestion, immune response, and muscle controland may help explain why certain diseases disproportionately impact specific populations.

This groundbreaking work builds on two pivotal milestones in genomics. In 2022, researchers achieved the first fully complete human genome sequence, filling long-standing gaps left by the original Human Genome Project. A year later, in 2023, scientists released a draft human pangenome based on 47 individuals marking a major advance toward capturing global genetic diversity. The new study goes even further closing 92% of the remaining gaps and offering an unprecedented view of genomic variation across human populations.

“For far too long, our genetic reference maps have left out much of the world’s population,” said Christine Beck, a geneticist at The Jackson Laboratory and UConn Health’s School of Medicine, who co-led the study. “This work captures vital genetic variation that helps explain why disease risk differs between individuals.

By unlocking DNA regions once considered too complex or variable to analyze, this study establishes a new benchmark for genome sequencing and pushes the field closer to a more comprehensive and inclusive understanding of human biology.

The project was a collaborative effort involving more than 20 institutions, including the University of Washington, European Molecular Biology Laboratory, Heinrich Heine University, University of Pennsylvania Clemson University, Yale University, and the University of Colorado, conducted under the Human Genome Structural Variation Consortium.

Hidden Within Our DNA

“It’s only in the last three years that technology has advanced enough to allow us to sequence entire human genomes,” said Charles Lee, a JAX geneticist and Robert Alvine Family Endowed Chair who first identified widespread structural DNA variation in 2004. 

DNA is decoded by reading the sequence of nucleotides—its fundamental building blocks—which function like letters in a manual directing every biological process. While current technologies can accurately read much of the genome they often struggle with long, repetitive, and complex sequences spanning millions of letters. These regions, known as structural variants, can elevate disease risk offer protective benefits or sometimes have no detectable effect at all.

Now, a landmark study led by JAX and UConn Health has decoded 1,852 complex structural variants across 65 diverse genomes, shedding light on previously hidden regions of DNA. The team resolved the complete Y chromosome from 30 males, the immune-linked MHC region and genes involved in diseases like spinal muscular atrophy and neurodevelopmental disorders. 

This work, powered by advanced sequencing and new software from JAX creates an open-source roadmap for decoding the most difficult parts of the genome and marks a major leap forward for precision medicine. As researcher Peter Audano put it: “We’re finally reading the missing pages of the genome.”

Source:https://today.uconn.edu/2025/07/the-most-complete-view-of-the-human-genome-yet-sets-new-standard-for-use-in-precision-medicine/#