The most complete map of human DNA is ready, opening the way to tailored medicine.

The most complete map of the human genome ever obtained opens the way to personalized medicine and tailored therapies, decoding complex, previously elusive DNA variations that influence a wide range of characteristics, from digestion to the immune response to muscle control, and therefore play a crucial role in many diseases.

This major advance in understanding the human genome is the result of two large-scale international studies published in the journal Nature and led by the European Molecular Biology Laboratory (EMBL) and the Heinrich Heine University of Düsseldorf, Germany. The new map builds on two key successes achieved in recent years: the first complete sequence of a single human genome, published in 2022, and the first draft pangenome representing global genetic diversity, obtained in 2023 from 47 individuals.

The new data

The new data, which have been made publicly available, significantly expand both efforts, filling 92% of the remaining gaps thanks to new technologies that allow much longer DNA sequences, up to tens of thousands of bases, to be read at once and interpreted correctly.

"About 15 years ago, most human genome sequencing was based on 'reads' of small stretches of DNA, insufficient to reconstruct a complete genome," says Jan Korbel of EMBL, who coordinated the researchers with Tobias Marschall of the University of Berlin. "However, for about five years now, it has become possible to systematically sequence human genomes thanks to new commercially available technologies," Korbel comments, "capable of decoding much longer stretches of DNA."

Genetic variations

Genetic variations contribute to making each individual unique. In their initial work, the research team examined 1,019 genomes from the 1000 Genomes Project dataset, spanning 26 populations across five continents. Using long-read sequencing methods, the researchers created detailed maps of structural variation in the cohort's genomes. "The original initiative," says Sarah Hunt, co-author of the research, "created a map of variable genome locations in the human population, and this allowed us to systematically search for regions associated with common diseases. Our version is more precise and in-depth and will allow us to search for new disease correlations."

The second research group relied on a sample of 65 individuals, but combined several powerful sequencing methods to assemble more complete genomes than previously possible. "This work," Hunt emphasizes, "reveals new biological insights, shedding light on parts of the genome we couldn't see before."

Genetic diseases

The findings are of enormous clinical significance, as they represent a benchmark for identifying and verifying genetic variations in diseases. In a third experiment, the researchers demonstrated that using the larger dataset, consisting of 1,019 genomes, significantly improved the accuracy of identifying disease-associated variants compared to previous methods. "These studies," Marschall concludes, "represent an excellent example of collaborative research that opens up new perspectives in genomic science and a step toward a more complete human pangenome."