People with two copies of the Δ32 mutation died at rates 21 percent higher than those with one or no copies – application of CRISPR @Berkeley
Reporter: Aviva Lev-Ari, PhD, RN
2.1.3.3 People with two copies of the Δ32 mutation died at rates 21 percent higher than those with one or no copies – application of CRISPR @Berkeley, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair
CCR5-∆32 is deleterious in the homozygous state in humans
Nature Medicine (2019)
Abstract
We use the genotyping and death register information of 409,693 individuals of British ancestry to investigate fitness effects of the CCR5-∆32 mutation. We estimate a 21% increase in the all-cause mortality rate in individuals who are homozygous for the ∆32 allele. A deleterious effect of the ∆32/∆32 mutation is also independently supported by a significant deviation from the Hardy–Weinberg equilibrium (HWE) due to a deficiency of ∆32/∆32 individuals at the time of recruitment.
CRISPR baby mutation significantly increases mortality
“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,” he said. “Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago.”
SOURCE
https://news.berkeley.edu/2019/06/03/crispr-baby-mutation-significantly-increases-mortality/
In the UK Biobank data they found two lines of evidence to suggest that these days, CCR5 actually is a net negative. In the first analysis they tracked how long people survived after enrolling in the Biobank study. They found that between the ages of 41 and 78, people with two copies of the Δ32 mutation had significantly higher death rates. They also observed that far fewer people with two copies enrolled in the study than expected, which they interpreted to mean that these individuals were less likely to survive into middle age than the general population. “Something has removed people with two copies of the mutation, and the likely explanation is increased mortality,” says Nielsen.
A child was born missing a large chunk of DNA in its CCR5 gene. This gene coded for a receptor on the surface of immune cells useful for coordinating responses to invading pathogens. And this spontaneous deletion torpedoed CCR5 production—one copy shrunk the number of receptors on cells, two copies erased the receptor altogether.
Today, the Δ32 mutation occurs in about 10 percent of the population of Europe, in a decreasing gradient from north to south. Natural selection pushed it through the population about 100 times faster than if it were a neutral change to the genome. But with the invention of vaccines, and the eradication of diseases like smallpox over the last century, the mutation has become less useful. According to Nielsen and Wei’s analysis, it’s now downright detrimental.
SOURCE
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