Last year, Chinese scientist He Jiankui shocked the world with the revelation the first ever CRISPR gene-edited babies had been born. It was revealed at least two babies had been born with explicit modifications to a gene called CCR5. A massive genome study by two scientists from UC Berkeley has found this CRISPR gene edit may be associated with a higher rate of early mortality in later life.
In the past, a natural genetic mutation in the CCR5 gene has been found to confer a resistance to the HIV virus, and He's research set out to replicate that specific mutation in human embryos. His work effectively replicated the mutation, which blocks the production of a protein that helps HIV infect immune cells.
One of the many controversies hovering over the project was the fact it was unclear exactly what the broader ramifications would be in altering the CCR5 gene in this way. Prior study had found that while this particular CCR5 mutation could thwart HIV infection, it also seemed to make individuals more susceptible to influenza and West Nile virus infection.
"Here is a functional protein that we know has an effect in the organism, and it is well-conserved among many different species, so it is likely that a mutation that destroys the protein is, on average, not good for you," explains Rasmus Nielsen, senior author on the new study. "Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago."
To better understand the broader ramifications of this particular CCR5 mutation, Nielsen and first author Xinzhu Wei scanned over 400,000 genomic records in the UK Biobank. The results showed people with two mutated copies of the CCR5 gene were 21 percent more likely to die before the age of 76 than individuals with either one copy of the mutation or no copies.
Another indication the specific CCR5 mutation could confer a higher mortality rate was the fact that a lower number of people with the gene mutation than expected were enrolled in the Biobank database. The average age of enrollment in the UK Biobank database is 56, so it is suggested the low rate of enrollments with CCR5 mutations could be attributed to a higher mortality rate.
"Both the proportions before enrollment and the survivorship after enrollment tell the same story, which is that you have lower survivability or higher mortality if you have two copies of the mutation," says Nielsen. "There is simply a deficiency of individuals with two copies."
It is unclear exactly why certain communities may have evolved, and preserved, this particular genetic mutation considering, on average, it results in higher mortality. This CCR5 mutation is naturally found in higher rates in Northern European populations, and rarely seen in Asian populations. However, Nielsen and Wei suggest there is little benefit to this mutation, and several potential harms.
"Beyond the many ethical issues involved with the CRISPR babies, the fact is that, right now, with current knowledge, it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do," adds Nielsen. "In this case, it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it."
The research was published in the journal Nature Medicine.
Source: UC Berkeley
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