In this week's PNAS Early Edition, a team led by investigators at the University of Pennsylvania School of Medicine reports on its functional screen of RNA-binding proteins in yeast. The team aimed to identify amyotrophic lateral sclerosis-associated candidates similar to those RNA-binding proteins, FUS and TDP-43, that were previously identified as associated with ALS. The team "performed a systematic survey of these proteins … followed by bioinformatics to predict prion-like domains in a subset of them," it writes, adding that it also sequenced one candidate gene, "TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls." In its in vitro analysis, the team found that like FUS and TDP-43, TAF15 aggregated; in a Drosophila model, the TAF15 variant conferred neurodegeneration. "We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery," the Penn team writes.
Elsewhere in the Early Edition, Memorial Sloan-Kettering Cancer Center's Luc Morris and his colleagues "present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components and [a] high-resolution genomic copy number assessment." Morris et al. report that "no point mutations were observed in other pathway genes such as PTEN and EGFR," as well as "frequent copy number alterations of … PIK3CA, EGFR, protein tyrosine phosphatase receptor S, and RICTOR."
In another paper published online in advance this week, investigators at The Malaria Institute at Macha in Choma, Zambia, and at the Johns Hopkins Malaria Research Institute in Baltimore, Md., show that Plasmodium falciparum "bear highly host-specific drug-resistant polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes." As such, the team suggests "it may be useful to sample both human and mosquito vector infections to accurately ascertain the epidemiological status of drug-resistant alleles."
An international team led by researchers at the Leibniz Institute for Zoo and Wildlife Research in Berlin this week shows that "genotypes of pre-domestic horses match phenotypes painted in Paleolithic works of cave art." By genotyping "nine coat-color loci in 31 predomestic horses from Siberia, Eastern and Western Europe, and the Iberian Peninsula," the team found that of the phenotypically diverse animals, "six shared an allele associated with the leopard complex spotting [or LP], representing the only spotted phenotype that has been discovered in wild, predomestic horses thus far." Overall, the team says "all horse color phenotypes that seem to be distinguishable in cave paintings have now been found to exist in prehistoric horse populations, suggesting that cave paintings of this species represent remarkably realistic depictions of the animals shown."