The most complete map of human DNA opens the door to personalized 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 immune response to muscle control, and thus play a crucial role in many diseases. This significant step forward 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, which have been made publicly accessible , 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 in one go 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."

The two studies combined different and complementary approaches to obtain the most complete and representative map of human diversity possible: the first sequenced the genomes of over 1,000 people from 26 different populations at medium-level resolution , while the second sequenced just a few genomes, 65 in total , but at a much higher level of detail . The researchers focused in particular on complex structural variations in the genome, in which large portions of DNA rearrange and fuse in unpredictable ways. Mapping these variations is incredibly difficult: it's like trying to make sense of the pages of a book after they've been torn out, reshuffled, and reassembled without being able to see the original version.

A total of 167,000 of these variants were found, doubling the number known to date. Approximately 3 out of 5 are found in less than 1% of individuals , a crucial level of detail for diagnosing rare genetic diseases . "This is an important step forward in mapping the blind spots of the human genome and reducing the bias that has long favored genomes of European origin," says Bernardo Rodríguez-Martín of the Center for Genomic Regulation in Barcelona, co-author of one of the two studies, " paving the way for therapies and tests that work equally well for people around the world."

The authors of the studies also managed to completely map , among other things, the Y chromosome, which until now has been particularly difficult to read due to the presence of many repetitive sequences, and a complex region of the human genome associated with the immune system and more than 100 diseases. "Now we can say 'here's a mutation, it starts here, it ends there, and this is what it looks like': it's a huge step forward," concludes Peter Audano of the US Jackson Laboratory, one of the researchers who participated in the project. "Now scientists studying autism, rare diseases, and cancer will have the tools to see everything that has eluded us for decades."