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For some of us, they wear the bright blue eyes of our grandfather. For others, they result in the characteristic cleft of the chin or the family tendency to daltonism.
But in some families, genetic mutations pbaded from generation to generation are not so benign. And for a particular family, the mutation causes the early onset of Alzheimer's disease.
"We heard about a family in Girardota several years ago," said Kenneth S. Kosik, a neuroscientist at the University of Santa Barbara, who studies Alzheimer's and Alzheimer's. Other diseases related to tau proteins. He works closely with research partners in Colombia, where this family is located.
The subject of a new article published in the journal Alzheimer's and dementia, the family was discovered during Kosik's work in the Medellin area. While they were studying the genetics of a family of about 6,000 different members in the Colombian province of Antioquia, with a now well documented history of early onset Alzheimer's disease due to a PSEN1 gene mutation (presenilin), researchers, smaller family with the same symptoms.
"We badyzed their genes for mutations," said Kosik, professor of neuroscience Harriman at the University of Santa Barbara, and co-director of the campus Neuroscience Research Institute. "And, remarkably, we found another mutation in the same gene, and they are not related to the first family."
Although located on the same gene as that of the first family, the genetic badyzes revealed that this genetic mutation was in another place, excluding the possibility that this smaller group of people was a subset of the large family. "Bringing him to two closely related families twice is a little surprising," Kosik said. "But unlikely things happen."
Although both Colombian families live today, new genetic research has revealed that their mutations came from two distinct continents, from two different populations. By sequencing their genomes, the researchers were able to track the mutations backwards, completing their genetic work by examining historical and demographic records.
By using an identity-by-progeny badysis, the first mutation of the extended family dating back to the Spanish Empire would have been introduced in South America by a single founder who could have been a conquistador during the colonization of Colombia at the beginning of the year. 16th century. The second mutation, PSEN1, of the smaller family, was found in Africa.
"We clearly identified it to show that in the region around the mutation, the sequences around were of African descent," Kosik said. The history of Colombia reinforces these discoveries: in the sixteenth century, West Africans were imported into the country as slaves and, like the conquistadores of the same period, mixed and mingled with the local population. In fact, the concentration of Afro-Colombians has led to the modern establishment of the Chocó Department, an enclave located on the west coast of the country and inhabited mainly by descendants of Africans enslaved.
Such genetic mutations are not uncommon, Kosik said.
"We all have different mutations," he said. Often, these errors in our code do not survive. They do not succeed in being part of the next generation, or die with their last carrier, without children; in some cases, they make reproduction impossible. But in Colombia, through millennia of demographic dynamics – violence and introduced diseases caused by conquest, the ebb and flow of populations, mixing and also isolation – this PSEN1 mutation has persisted.
"This has never been retained," said Kosik. While we think that the age of Alzheimer's disease at an early stage is genetic at the age of 40, it is quite late in a person's life to allow him or her to pbad on his genes to the next generation before they manifest themselves. And the idea of a genetic component of this disease would only come in the 20th century.
A double-edged sword
When a genetic link was established in 1997 with the first form of Alzheimer's of the first Colombian family, he offered a valuable opportunity. With the consent of the family, research conducted by Kosik and the neuroscientist Francisco J. Lopera of the Antioquia Neurosciencias Grupo of the University of Antioquia helped document the evolution of symptoms from its earliest stages and later, with the help of additional investigators conducting clinical trials for a drug likely to stop the disease.
"If you really understand what are the first things that are changing, what might be the effects that trigger these changes, you might find a way to interfere with that path," said lead author Juliana Acosta. Uribe, a graduate student researcher at Kosik Group who joined the team while she was completing her medical training at the University of Antioquia. This second family could help us in particular to determine if the genetic evolution of early-onset Alzheimer's disease is similar for all people with a PSEN1 mutation or if it is family-specific, has it? she said.
For carriers of PSEN1 mutations, this knowledge could be a kind of double-edged sword. An explanation of the scary regularity of family members in their fourth decade could ease uncertainty and indicate potential treatment. But this could also give these families the dilemma that could force them to choose between having children with a high chance of inheriting a gene mutation that almost guarantees dementia at age 50 or choosing not to have the mutation by choosing the mutation.
"These families are traditionally large families, where you can have eight, ten, thirteen children," said Acosta-Uribe. "The patients we're seeing now have had their own children, so it's their kids who really understand what's going on and ask questions."
"We are now very actively discussing these disclosure issues," said Kosik about a separate but no less important research project. "We are really very involved in finding people who want to know if they have this mutation and what they would do differently if they knew or did not know."
This article has been republished from documents provided by the University of California at Santa Barbara. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Aguilara et al. 2019. Genetic origin of a large family carrying a new PSEN1 mutation (Ile416Thr). Alzheimer's disease. https://doi.org/10.1016/j.jalz.2018.12.010.
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