After 21 years, the map of the human genome has been completed: six articles published in a special issue of the magazine “Science”, which dedicates the cover to this milestone, bring to light the content of 8% of the book of life which until now was not been decrypted. “We are seeing chapters that have never been read before,” the researchers write. The result is due to the international consortium called Telomere-to-Telomere (T2T) and is an unprecedented step in supporting frontier fields, such as personalized medicine, population genome analysis and the possibility of rewriting DNA.
In addition to deciphering the 8% of the genome that was missing, the new map fills many gaps, spaces in the book of life left blank and marked so far with the letter N, indicating that to unknown elements. In this way, compared to the 2001 version, the complete map of human DNA includes as many as 200 million more letters, which in total are equivalent to the information contained in a chromosome. It was like having a map of New York without Manhattan, the researchers note. The missing parts include sequences that are repeated many times and that now acquire a greater importance than previously thought. It is in the repetitions that the secret of human diversity hides, observes geneticist Rachel O’Neill, of the American University of Connecticut and scientific director of the T2T project. Uncovering this still hidden side of human DNA took more than 20 years because “it took new methods of DNA sequencing and computational analysis,” notes geneticist Francis Collins, scientific advisor to the White House and former director of the National Institutes. of Health (Nih). “It was worth the wait,” he adds, because “a variety of surprising architectural features are now emerging, with important consequences for the understanding of human evolution, variation and biological function.”
«Since we obtained the first draft of the human genome sequence – says Evan Eichler, of the University of Washington – determining the exact sequence of complex genomic regions has been challenging. We are really enthusiastic about this goal, even if we still have many questions to solve ». «Thanks to long-reading methods – observes Karen Miga, co-chair of the T2T consortium and researcher at the University of California at Santa Cruz – we have made progress in our understanding of the most difficult and repetitive parts of the human genome. This sequence has already provided new information on the biology of the genome and we are really curious to know what else it will be possible to understand thanks to this information ».
“It’s like having a DNA vocabulary”: for the geneticist Giuseppe Novelli, of the University of Rome Tor Vergata, this is the great advantage of having a complete map of the human genome: “we have terms of reference that finally make it possible to do the diagnosis of some diseases “. These are rare diseases, generated by unstable genetic sequences. “Last July – continues Novelli – the Telomere-to-Telomere (T2T) consortium had published reference standards”, that is, it had developed protocols to obtain the external sequencing of long DNA fragments. “It is possible to read fragments of this type only with machines suitable for this purpose,” said Novelli. “Even in Italy we have laboratories capable of doing this, but so far there was no standard of comparison”. Having this sort of dictionary of long unstable DNA sequences now available could make it easier to diagnose certain diseases, such as mental retardation due to Martin Bell syndrome, characterized by long fragments of genetic information with interruptions in a repeating segment. «It is not enough to sequence the DNA: you have to know how to read it and you have to interpret it. Otherwise, it is very difficult to diagnose diseases due to repeated sequences, with interruptions that in the past could not be seen ».