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Thomas Drake and colleagues report the results of knockout or transgene introduction for nine obesity candidate genes in mice. Eight of the nine mutations result in significant changes in obesity-related traits, validating their previously developed approach for identifying candidate genes involved in particular phenotypes. They further identify related metabolic pathways that are altered by manipulation of the eight genes.
Eran Segal and colleagues report that promoters driving expression of cellular respiration genes in aerobic yeast species encode relatively open chromatin, whereas promoters associated with the same genes in anaerobic yeast species encode relatively closed chromatin. These results suggest that phenotypic diversity may in part be influenced by changes in the DNA-encoded nucleosome organization of promoters.
Ernest Fraenkel and colleagues present ResponseNet, a method used to integrate analysis of genetic and transcriptional datasets, and its application characterizing yeast cellular responses to alpha-synuclein toxicity.
Trudy Mackay and colleagues present a resource of 40 Drosophila melanogaster wild-derived inbred lines. The authors quantify genome-wide variation in transcript abundance for six ecologically relevant traits, characterize the transcriptome and identify transcriptional modules.
Haruhiko Koseki and colleagues identify a gain-of-function mutation in Fgf9 in mice with elbow knee synostosis. They further show that this mutation prevents homodimerization of Fgf9, allowing increased diffusion of the altered protein through developing tissues.
Susan Lindquist and colleagues report a genetic interaction between α-synuclein and the ortholog of human ATP13A2 (PARK9) in yeast, two genes that when mutated cause Parkinson's disease. They further show that yeast PARK9 protects cells from manganese toxicity, a known environmental risk factor for Parkinson's disease.
Andy Feinberg and colleagues show in a colon cancer model that most DNA methylation alterations occur in sequence regions distinct from promoters or canonical CpG islands, termed 'CpG island shores', and that this methylation is strongly related to gene expression and can discriminate tissue types regardless of species of origin.
James Lupski, Orly Reiner and colleagues report seven individuals with submicroscopic copy number gains in the 17p13.3 region, supported by additional studies in transgenic mice. Duplications overlapping PAFAH1B1 (encoding LIS1) were associated with mild brain structural abnormalities, moderate to severe developmental delay and failure to thrive.
