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This Week in PNAS: Aug 26, 2014

In the early edition of the Proceedings of the National Academy of Sciences, researchers from the UK, the US, and the Netherlands critique a PNAS study, published last year, which had claimed to find links between shifts in immune gene expression — including elevated expression of pro-inflammatory genes — and psychological well being. The authors of the re-analysis argued that the statistical methods used in the original study were flawed, leading to misleading conclusions based on analytical artifacts. Moreover, they say, "our findings may have implications for the re-evaluation of other published genomics research based on comparable statistical analyses."

A Broad Institute-led team used targeted gene sequencing to track down rare variants in a peroxisome-related gene called PPARG that contribute to type 2 diabetes risk. Based on prior studies showing ties between diabetes-related traits such as insulin resistance and familial PPARG mutations, the researchers sequenced the peroxisome proliferator-activated receptor gamma-coding gene PPARG in 9,01track down rare variants0 individuals with type 2 diabetes and 10,682 unaffected controls. The search led to 49 non-synonymous PPARG variants with suspected type 2 diabetes ties. As a group, these alterations weren't associated with type 2 diabetes risk, though follow-up experiments in human fat cells suggested that a subset of variants that dialed down adipocyte differentiation were also linked to enhanced type 2 diabetes risk.

Viral sequence elements in the ground squirrel genome appear to have been co-opted to thwart the replication and successful infection by bornaviruses, according to another PNAS study. Researchers from Japan and the US scrutinized a so-called endogenous bornavirus-like element — a fragment of expressed sequence that closely resembles the bornavirus nucleoprotein — in the genome of the thirteen-lined ground squirrel Ictidomys tridecemlineatus. When they cloned this itEBLN element and tracked its activity in human cell lines infected with Borna disease virus, the study's authors saw a decline in viral replication via interference with the Borna disease virus polymerase. "To our knowledge," they write, "this is the first report showing that endogenous non-retroviral RNA virus elements may function in antiviral defense, providing a potential role for RNA virus endogenization in host evolution."