In the early, online edition of the Proceedings of the National Academy of Sciences, an international team led by investigators in Singapore and the US presents results from a mutagenesis screen intended to root out mutations that contribute to gastric cancer development in mice missing one copy of the tumor suppressor gene Smad4. Using Sleeping Beauty transposon mutagenesis coupled with transposon insertion sequencing in 66 gastric tumor samples from Smad4-mutant mice, the team uncovered 59 genes suspected of driving gastric cancer development, including several genes or pathways implicated in studies of gastric cancer in humans. And by comparing data from their screen with sequences for hundreds of human gastric tumors generated for prior studies, the authors narrowed in on an apparent tumor suppressor role for the LDL receptor-related protein 1B gene LRP1B.
Australian researchers take a look at factors that may influence the transmissibility of so-called spillover viruses that humans are exposed to through contact with animal reservoir hosts. The team scrutinized everything from viral genome length, structure, and type to host infection and mortality features for more than 200 DNA or RNA viruses — a set that included 105 viruses capable of human-to-human transmission. Its results suggested that genome features such as length, DNA or RNA type, and recombination frequency had relatively little impact on how prone a virus was to become transmissible, while the transmissibility potential appeared to be higher for viruses associated with low host mortality, the presence of chronic infection, and biological features such as non-segmentation and a lack of vector intermediate.
Finally, a team that includes members of the IMAGEN consortium reports on findings from a study of genetic determinants that mediate reward processing in the brain. Using a genome-wide association study approach, the researchers searched for genes contributing to particular reward network nodes and connections in more than 1,500 adolescents whose network activation had been assessed using functional MRI neuroimaging. In additional to identifying a striatal network node suspected of coinciding with adolescent hyperactivity, for example, they linked these neurobehavioral features to a gene called Vps4 that was subsequently tested for its role in hyperactivity in Drosophila.