Genetics becomes more inclusive: the catalog of changes in the human DNA in the different populations expanded, to get to know us (and take care of) better.
Two new studies just published on Nature They provide the most detailed overview ever obtained so far on human genetic diversity. By decoding the differences in the DNA sequence between individuals in the most difficult regions to sequence, the two research will allow to understand why certain diseases affect certain populations more than others.
Decipher the DNA: the steps taken up to here
In 2001 the human genome project (Human Genome Project), one of the most important international scientific initiatives of modern times, succeeded in the extraordinary undertaking of reading and sequencing the approximately 3 billion letters that make up our DNA, producing a genomic sequence that represented over 90% of the human genome: the maximum that the DNA sequencing technologies allowed at the time.
The remaining gaps were filled in 2022, when the Telomere-to-nomere international consortium (T2T) announced that they had produced the first truly complete sequence of the human genome. However, to really understand what differentiates from other individuals and represent human genetic wealth, that is, the many possible ways for our genes to carry out the same task, a more representative and inclusive sample was needed of the genetics of our species. With this intent, in 2023 a draft of pangenoma was published, built starting from the DNA of 47 individuals of different origin.
Deep differences
In the last 5 years, progress in sequencing technologies have made it possible to decode much longer DNA traits and to map the so -called structural variations, long, complex and highly repetitive segments of millions of letters (nucleotids) DNA that can present themselves deleted, inverted, repeated or added.
These different ways that DNA has to reorganize are common and influence the functioning of the genes. They therefore play an important role in the genesis of common diseases, such as cancer, but also of rarer conditions, such as some neurodegenerative diseases; They guide common biological processes, such as immune or digestive ones, and have produced significant changes during human evolution.
Two complementary approaches
In the first study, the European Laboratory of Molecular Biology (EMBL) of Heidelberg, Germany, collaborated with the Institute of Molecular Pathology (IMP) of Vienna, in Austria to analyze 1,019 genomes taken from the dataset of the 1000 Genomes Project, representatives 26 populations of five continents.
The researchers used the genetic sequencing methodologies of long portions of DNA to catalog the structural variations in the genomes of these individuals, doubling the note of the known structural variation already identified in the human pandenoma. The authors call it an important step “to reduce the basic error that has long favored the European descent genomes and opens the way to therapies and tests that work equally well for people around the world”.
The second study, conducted by the Ambl scientists together with researchers from several important US institutes, used a smaller champion, of only 65 individuals of various origins, but with a much greater sequencing power, to solve and destroy 1,852 complex structural variants previously unreliable and therefore hidden. Those who were once considered “blind points” of genetics have now been transformed into precious sources of information. The scientists have in fact shared their structure in Open Source so that it can be consulted by any researcher, as per those involved in rare genetic diseases.
For example, the variants in a group of genes have been completely resolved, known as the largest complex of histocompatibility, associated with the immune system and connected to cancer, autoimmune diseases and a hundred other pathologies. But genetic regions target of life -saving therapies against spinal muscle atrophy, a genetic disease that affects cells that control muscle movements, and mobile elements that can jump along the DNA and modify the behavior of the genes (transposons).
The study also contributed to a better knowledge of the centromers, DNA sections very difficult to study, where the two filaments of a chromosome attack each other, forming the well -known X shape: variants in these regions are connected to immune and cancer diseases.