Surprising in the nucleus

Partial translation:

»Contrary to previous assumptions, human body cells do not carry a uniform genetic make-up, but form mosaics. This could explain many diseases.

Genetics has been keeping a dirty little secret for a long time. Now it can no longer be concealed. It has become too big. Of all things, the discipline's most recent successes threaten to topple one of its central pillars. The textbook knowledge that all human body cells harbour an identical genome is proving to be a fundamental error.

The idea that there were no - if any - significant genetic differences between the body's cells was once a credo of biomedical research. It was known that during growth there are always errors during cell division, i.e. that the genetic material of the daughter cell is never completely identical to that of the mother cell. But the problem was never taken seriously.

In any case, there was no technique that would have allowed the examination and comparison of individual cells. To break down a single hereditary molecule, researchers need many copies of it. In the past, they simply extracted the genetic material from various easily accessible tissues, for example from the blood or the oral mucosa. This way, the experts thought, they would also have the genetic information from all other body cells at hand - for example, from those in the brain or in the liver...

This fallacy has persisted for decades. In the belief that they were identical copies, scientists examined samples containing millions of cells. Differences were lost in this mass. In the meantime, however, there are decoding methods with which even the genetic material of a single cell can be reliably multiplied and examined in the laboratory. This provides a far more detailed picture. It turns out that in reality no two cells are alike...

It is now unmistakable that the genome of a human being is not stable, but is constantly changing. During the countless cell divisions that build up the nascent life, the structure of the human source code changes. Soon, the body will no longer be governed by a uniform set of hereditary data, but rather by a patchwork of cell assemblies with diverse gene configurations. In September, the research guild met in Heidelberg to take stock - motto: "The mobile genome".

The first facets of the mosaic already emerge in the fertilised egg. Even during the first cell division of the embryo, information can be shifted, lost or multiplied. Then this person later carries the new deviations in half of his body cells, namely in all the offspring of the one changed daughter cell of the egg. The later in development such mutations occur - and apparently this happens all the time - the fewer cell groups are ultimately affected in the adult body.

Genomic diversification seems to occur particularly blatantly in the developing brain. The result: colourful chaos reigns there, even in healthy humans. The thinking organ is a genetic patchwork.

The genetic unit of the human being has disintegrated

With the new state of knowledge, the last order variable has disappeared from human genetics. Shortly after the first deciphering of the human genome in the Human Genome Project about 15 years ago, it had already become apparent: The universal genome of our species is a fiction. When geneticists decoded the genome of more and more individuals, they already discovered the first astonishing differences. And an international research consortium has just taken stock of its seven-year 1,000 Genomes Project on hereditary data from around 2,500 healthy people from all continents. Once again, genetic variations were found everywhere.

Now the genetic unit of the human being is also disintegrating, the biological identity of the individual must be abandoned: "Our genome has fallen" - US researchers Evan Macosko and Steven McCarroll lamented the fall of the icon of their field. The concept of genome turns out to be a rickety construction of human thought from the outset. A person's genome simply does not exist - the body is a randomly generated mosaic of many genomes...

Particularly in medical research, it is important to rethink the state of knowledge; quite a few findings must now be placed under reserve...

... Perhaps human geneticists have been searching for decades in the blood of their patients for causes of their suffering that do not exist there at all, but only in the hereditary molecules of the brain cells. And there the terrain is unmapped.

Neuroscientist Thomas Insel, director of the American National Institute of Mental Health, was the first to dare to confront his colleagues in the field with the upheaval. The search for genetic causes of neuropsychiatric diseases has been based on the assumption that every cell in the body has the same genetic material, Insel wrote in the journal Molecular Psychiatry. "This assumption is wrong." For the time being, there is perplexity in the face of the unexpected diversity in the gene code. The neuroscientist notes that we are "faced with the dark matter of genetics".«

Source: https://archive.ph/7j8jh