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This Week in PNAS: Jan 6, 2015

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.

In a study slated to appear online this week in the Proceedings of the National Academy of Sciences, the University of Edinburgh's Brian Charlesworth uses data from Drosophila fruit fly populations to explore interrelationships between genetic variation, fitness, and selection. By bringing together population data looking at fruit fly quantitative genetics and fitness components, his computational analysis considered the interplay between fitness effects of genetic variants and the apparent strength of selection acting on such variants, leading Charlesworth to conclude that "the mean selective effect of a new, mildly deleterious mutation in Drosophila is greatly underestimated by recent analyses of DNA sequence polymorphism data."

Researchers from Emory University School of Medicine and Washington University describe a missense mutation in the fragile X mental retardation 1 (FMR1) gene that appears to specifically alter pre-synaptic activity of the resulting protein. The team focused on a missense mutation previously detected in an individual with intellectual disability, developmental delay, and intractable seizures. From their protein interaction and functional experiments in mouse models and cell culture, the investigators found that the mutation in question did not seem to interfere with FMR protein's RNA binding or translational duties. Rather, it upended the protein's pre-synaptic interactions in ways that seem to impact neuronal action potential, they report.

Finally, a team from Uganda, the UK, and the US report on findings from a genetic study of preeclampsia, a placental defect condition that contributes to high rates of maternal mortality in sub-Saharan Africa. Using PCR-based genotyping, the researchers looked at variant profiles in the maternal immune gene KIR and the fetal human leukocyte antigen gene HLA-C in samples from 484 Ugandan women with preeclampsia and 254 women without. Their results pointed to KIR variants that appear to dial down preeclampsia risk in women from populations in sub-Saharan Africa, though follow-up analyses argue against such a protective effect in European populations.