Researchers Discover Thousands of Hidden Genetic Changes Using Long-Read DNA Sequencing

TAIPEI, TAIWAN, Jul. 31th, 2025- In a major scientific breakthrough, researchers have used advanced DNA sequencing tools to uncover thousands of previously hidden genetic variations in people from around the world. These discoveries mark a significant step forward in understanding how human DNA differs across populations—and how those differences may impact health and disease.

The findings come from two large international studies that focused on data from the 1000 Genomes Project, a global effort to study human genetic diversity. Until recently, scientists relied on older technologies that could only read short fragments of DNA, which made it difficult to detect certain types of genetic variation. Thanks to long-read sequencing, scientists can now analyze much longer and more complex pieces of the human genome.

This new method makes it possible to detect structural variants—large-scale changes in DNA such as insertions, deletions, and rearrangements—that play an important role in gene function and disease risk. These variants can range from a few hundred to millions of DNA letters long and were often missed by previous technologies.

In the first study, researchers used long-read sequencing on more than 1,000 individuals from 26 diverse populations in Africa, Asia, Europe, and the Americas. This allowed them to identify over 167,000 structural variants, with each individual carrying between 15,000 and 21,000 such changes. Strikingly, over half of the insertions and more than 14 percent of the deletions had never been recorded before.

To help with this complex analysis, the team used a new computer method that organizes the genome using a graph-based approach. This made it easier to track down variations, even in regions of the genome that are difficult to read. The result is one of the most comprehensive maps of structural variants ever produced.

This high-resolution view of the human genome builds on previous efforts, such as the Human Pangenome Reference Project. With more than 1,000 samples now studied in such detail, scientists are better equipped to explore how these genetic differences might contribute to common and rare diseases.

In a follow-up analysis, the researchers examined four individuals diagnosed with rare diseases and discovered an average of 386 potentially disease-related variants per person. This included changes in over 270 genes known to be linked to health conditions—many of which occur in parts of the genome that were previously hard to study.

A second study took a different approach: instead of analyzing thousands of genomes at lower depth, scientists fully or nearly fully sequenced the genomes of 65 individuals from more than two dozen populations. Using a combination of long-read sequencing and other advanced tools, they created 130 detailed genome "assemblies"—essentially putting together complete maps of both copies of each person’s genome.

These genome maps revealed more than 26,000 structural variants per individual. The team also studied hard-to-sequence regions like the major histocompatibility complex, which plays a crucial role in immune response, and the Y chromosome, which is often difficult to analyze because of its repetitive structure. They successfully assembled the Y chromosome from end to end in six individuals, a rare achievement.

The research also provided new insight into parts of the genome where mobile elements—pieces of DNA that can move around—insert themselves. In total, the scientists identified nearly 13,000 of these insertions, offering new clues into how the human genome evolves.

Collectively, these studies provide one of the most detailed insights into human genetic variation to date. The data will serve as a valuable resource, inspiring and guiding future research across a wide spectrum of diseases, from cancer to neurological disorders to rare diseases [4], instilling a sense of hope and inspiration in the scientific community.

By integrating long-read sequencing with robust data analysis tools, scientists are not only enhancing our understanding of human DNA but also paving the way for personalized medicine and improved treatments in the years to come. This potential for personalized medicine is not just a promise, but a reality that is within our reach, sparking optimism and excitement in the scientific community.

Reference:

[1] Long-Read Sequencing Reveals New Structural Variation Details in 1000 Genomes Project Samples

[2] 1000 Genomes Project

[3] Long-Read Nanopore Sequencing Boosts Structural Variant Analysis in 1000 Genomes Project Dataset

[4] Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies

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