Scientists claim to have finally assembled the entire genetic blueprint for human life, adding the missing pieces to a puzzle nearly completed two decades ago.
An international team described the first sequencing of a complete human genome – the set of instructions to build and maintain a human being – in research published in May 2021 in the repository bioRxivwithout review by other researchers.
Now is when it is collected in six articles in the magazine Science, in addition to a dozen complementary writings in other scientific publications.
This is the first complete sequence that covers each chromosome from end to end, without gaps and with unprecedented precision. In addition, it is accessible to the entire scientific community.
The earlier effort, celebrated around the world, was incomplete because the DNA sequencing technologies of the time were unable to read certain parts. Even after updates at the time, about 8% of the genome was missing.
Map without “cracks”
The new “seamless” map of our DNA reveals hidden regions important for understanding genetic disease, reproduction, human diversity and even the evolution of our species: “truly finishing the sequence of the human genome has been like putting on new glasses “, summarizes researcher Adam Phillippy.
Behind this scientific milestone is the T2T (Telomere to Telomere) Consortium, with more than one hundred researchers led by Phillippy, from the National Human Genome Research Institute (NHGRI), and Karen Miga, from the University of California-Santa Cruz, in USA
The “dark matter of the genome”
Some of the genes that make us unique as humans were in this “dark matter of the genome” and were completely lost,” said Evan Eichler, a University of Washington researcher who was involved in the current effort and in the Human Genome Project. “It took us more than 20 years, but we finally got it.”
Many – including Eichler’s own students – thought it was over. “I was teaching them and they were like, ‘Wait a minute. Isn’t this the sixth time you’ve declared victory? I said, ‘No, this time we really did it.'”
New era of medical discoveries
The scientists claimed that this complete picture of the genome will give humanity a greater understanding of our evolution and biology, while also opening the door to medical discoveries in areas such as ageing, neurodegenerative conditions, cancer and heart disease.
“We are expanding our possibilities to understand human diseases,” said Karen Miga, an author of one of the six studies published Thursday.
“In the future, when a person’s genome is sequenced, we will be able to identify all the variants of their DNA and use that information to better guide their medical care,” Phillippy said in an NHGRI note: “Now that we can see everything clearly we are one step closer to understanding what it all means”.
“The parts of the genome that we had not been able to study for more than 20 years are important for understanding the functioning of the genome, genetic diseases, and human diversity and evolution,” says Miga.
Genome: set of instructions for an organism
The genome is an organism’s complete set of instructions, a book that is written with combinations of just four chemical units designated by the letters A, T, C, and G (adenine, thymine, cytosine, and guanine); these are called nucleotide bases.
For humans, this instruction manual contains some 3 billion base pairs (or letters), which are found in the 23 pairs of chromosomes within the nucleus of all cells. Sequencing means determining its exact order in a segment of DNA.
The version without “gaps” of the new reference genome –called T2T-CHM13– is made up of 3,055 million pairs of nucleotide bases and 19,969 genes that code for -producers- of proteins, the fundamental pillars of all the components of the organism. They do most of the work in cells and are necessary for the structure, function, and regulation of tissues and organs.
Of the protein-coding genes, the consortium found about 2,000 new ones, most of them deactivated, although a few hundred may still be active, that is, producing proteins. In addition, more than 2 million previously unknown genetic variants were discovered in those dark regions, 622 of which occur in medically important genes.
The researchers generated the complete genome sequence using a special cell line that has two identical copies of each chromosome, unlike most human cells that carry two slightly different copies.
Never-before-seen details around the centromeres
Among other things, the newly added DNA sequences reveal never-before-seen details around the centromeres, sections in the middle of chromosomes that play a fundamental role in their structure and in their proper segregation during cell division.
It has long been known that centromeres are poorly regulated in all kinds of diseases and now “for the first time we can study the sequences that define these structures ‘base by base’ and begin to understand how they work”, explains Karen Miga.
FEW (EFE, AP)