"Being born with an old father is more dangerous than being born with an old mother", warns Kári Stefánsson. It is not a revelation for specialists, but the team of this Icelandic geneticist has determined it with amazing precision. His group, armed with DNA data from some 150,000 Icelanders, has produced "the most detailed genetic map of the human genome" to date. "It's like moving from a paper road guide to Google Maps," sums up the geneticist Alberto M. Pendás, that has not participated in the investigation.
Genetic diversity is fundamental for human evolution, as the history of the Spanish monarchy demonstrates. The cousin sex custom of the House of Habsburg increased more than 13% mortality of the children of the dynasty, who ruled Spain between 1516 and 1700. Inbreeding is also a problem in the homeland of Stefánsson. Almost all of Iceland's current 340,000 inhabitants are more or less close relatives of the singer Björk.
The instruction manual of the human being is written in the genes, which are stretches of the long strands of DNA called chromosomes. Each person has 23 pairs of chromosomes in each cell of their body: in each pair, one comes from the father and one from the mother. During the formation of ovules and sperm, these paired chromosomes are aligned and allow an exchange of genetic material. The phenomenon, called recombination, is one of the two basic mechanisms to promote human diversity, that each person is unique.
"It's like moving from a paper road guide to Google Maps," summarizes geneticist Alberto M. Pendás
The second mechanism is the new mutations: genetic alterations that appear in a person without being inherited from their family. The map of Stefánsson, published today in the magazine ScienceIt is huge. It shows the precise location of 4.5 million recombinations and 200,000 new mutations.
Stefánsson, president of the Icelandic company of CODE, attacks "the classic premise that evolution is driven by random genetic changes". If recombination is like mixing a deck of DNA cards into ovules and sperm, the new map reveals a certain organization. "We have identified 35 genetic variants that influence recombination rates and the locations in which they occur. And we see that the new mutations are 50 times more likely in the places where recombination occurs than in other parts of the genome, "explains Stefánsson.
This genetic diversity, facilitated by the human genome itself, is essential for the success of our species, but it has a price for some people: the possible appearance of mutations that cause rare diseases. For the Icelandic geneticist, it is "a collective responsibility" to seek solutions to these infrequent pathologies. "80% of the new mutations come from the father. And they are the main source of rare diseases in childhood, "says Stefánsson." Down syndrome usually comes from the mother, but the father's mutations are more common and lead to disorders such as autism and schizophrenia, "he says.
"To look for fragments of the human genome associated with diseases, we need accurate maps. And this is the most accurate to date, "celebrates Arcadi Navarro, a researcher at the Center for Genomic Regulation of Barcelona, who is not aware of the new study. "This map does not indicate where a bag of oil is approximately, but it shows where the well is with a precision of meters," he explains with a metaphor.
Alberto M. Pendás studies genes involved in reproduction at the Cancer Research Center of Salamanca. "The rate of spontaneous mutation de novo in the gametes of men, sperm, is much greater than that of women. In addition, in men increases with age because the sperm come from progenitor stem cells-present in the testicles-which are dividing from adolescence to virtually the death of the individual, "he says. "It is much more dangerous to have an old father than an old mother. Much more ", ditch.