The largest atlas of human genetic mutations completed: based on the analysis of the tissues of hundreds of healthy donors, it allows for a better understanding of the molecular basis of conditions related to cellular malfunction (including aging) and paves the way for the possibility of diagnosing and treat many genetic diseases.
The result is published in the journal Science by the American Oregon Health & Science University.
The new atlas allows you to have a
broad overview of the genetic alterations
that can arise in the course of life, as cells multiply and accumulate errors in DNA replication, creating a real
genetic mosaic
.
To reconstruct it, the researchers started from
54 tissues and cell types
taken from
948
deceased people who had donated their bodies to science.
Thanks to a new computational method that has made it possible to analyze the data obtained with massive RNA sequencing, it has been possible to trace a sort of developmental tree on which the onset of mutations in the various tissues of people has been mapped.
"This study reveals that
the human genome is more dynamic than we thought
", comments Giuseppe Novelli, geneticist of the University of Rome Tor Vergata. "It demonstrates in fact that a certain percentage of mutations that we thought arise during the formation of gametes (ova and spermatozoa) actually appear after fertilization and the formation of the zygote.
As the contribution of such mutations to human disease becomes increasingly apparent, this conclusion may well have clinical implications.
It also reminds us that
a genetic test is not a simple laboratory test
, but requires complex evaluations and analyzes such as the simultaneous study of multiple tissues of the same individual". The US research also shows that
many mutations arise systematically
and in a certain predictable sense
with the
, while
about 10% seems to be determined by an intrinsic cause
, linked to the genes themselves or to the influence of the environment.
"We've learned that
some tissues
, such as those in the
esophagus
and
liver
,
acquire many mutations
while
others
, such as the brain,
acquire fewer
", notes the first author of the study, Nicole Rockweiler. "This makes sense - she adds - because the esophagus and the liver are exposed to many toxins of environmental origin and their cells must transmit their message in a 'noisy' environment.
Even the few mutations in the brain make sense, because the brain is basically made up of cells that don't replicate themselves". All this information could have an impact in the future on the way many diseases are treated. "Today there are many technologies that allow us to modify the genome," concludes study coordinator Don Conrad. "It may become possible to correct mutations that we have acquired through bad luck or bad habits."