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This Week in PNAS: Mar 7, 2017

In the early, online version of the Proceedings of the National Academy of Sciences, a German-led team reports on a SERPINA1 gene variant that appears to contribute to large artery atherosclerotic stroke risk. Through a genome-wide association study focused on protein-coding sequences in 3,127 individuals with large artery stroke and 9,778 unaffected control individuals, the researchers verified a prior association between large artery stroke risk and the HDAC9 gene, while closing in on a non-synonymous variant in SERPINA1. Their follow-up analyses of the latter association provided insights into interactions between the alpha-1 antitrypsin protein encoded by SERPINA1, the neutrophil elastase enzyme, and lipoprotein particles.

Researchers from the US and Russia report on findings from a comparative genomic analysis of cyanobacterial species in the Moorea genus, aimed at understanding the marine microbe's natural product repertoires. The team began by sequencing the filamentous, tropical marine cyanobacteria M. producens PAL from the Palmyra Atoll, before comparing the sequences with new draft genomes for M. producens and M. bouillonii strains from Jamaica, Curacao, and Papua New Guinea. "Our analyses revealed a vast and distinctive natural product metabolic potential in these strains," the authors write, "highlighting that they are still an excellent source of unique metabolites despite previous extensive studies."

An international team led by investigators in Singapore describes findings from a genetic screen for breast cancer susceptibility genes in mice. After identifying mice with breast tumors induced with Sleeping Beauty transposon mutagenesis, the researchers used deep sequencing to tease out transposon insertion sites in nearly three dozen mouse mammary tumors. The search led to 129 insertion hotspots in 134 potential breast cancer susceptibility genes — a set that included genes with human orthologs already implicated in breast cancer. With their subsequent network and survival prediction analyses, the investigators went on to present prognostic classifiers for human breast cancer subtypes.