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PNAS Studies on Indigenous Brazilians, Optogenetic Gene Editing, Asthma Treatment Response

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

A team from Brazil, Spain, and the US shares results from a population genomics study on indigenous individuals who trace their ancestry to Tupí-speakers who moved from the Brazil's Amazonian basin to the coast some 2,000 years ago and since disappeared from that area. Using array-based genotyping, the researchers profiled 102 Native Americans from Brazil, including almost four dozen admixed individuals of self-reported Tupiniquim communities. When they analyzed the genetic data alongside publicly available sequences for indigenous Brazilians, the authors got a look at population relationships and migration histories in Brazil, and found that Tupí ancestry persists in the Tupiniquim population. "We demonstrated that the Tupiniquim Native American ancestry is not related to any extant Brazilian Native American population already study, and thus could be considered the only living representation of the … Tupi branch that used to settle the Atlantic Coast of Brazil."

Zhejian University researchers outline a programmable genome-editing approach that relies on CRISPR-Cas9 tools in a nanosystem controlled optogenetically. The "nanoCRISPR" approach includes a heat-inducible promoter for Cas9 endonuclease enzyme on a plasmid, along with a nanorod delivery platform designed to tap into external energy — particularly near-infrared light — and convert it into the heat needed to prompt Cas9 expression, the team says. For their proof-of-principle experiments, the authors applied a photothermal nanoCRISPR strategy to mice with fulminant hepatic failure, showing that the gene editing approach could be used therapeutically in that model. Based on such results, they suggested that the optogenetically-activated CRISPR-Cas9 nanosystem "offers a useful tool to expand the current applications of CRISPR-Cas9, and also defines a programmable genome-editing strategy toward high precision and spatial specificity."

Meanwhile, a Cleveland Clinic-led team presents evidence suggesting altered androgen production may impact not only lung function, but also response to glucocorticoid treatment in individuals with asthma. Using available sequence data from the Severe Asthma Research Program, the researchers genotyped the adrenal androgen production-related gene HSD3B1 in hundreds of individuals with asthma, demonstrating that those with an "adrenal restrictive" version of the enzyme-coding gene with reduced androgen production coincides with resistance to glucocorticoid treatment.  "Our results suggest opportunities for prediction of [glucocorticoid] resistance and pharmacologic intervention," they write. GenomeWeb has more on the study, here.

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