In the early online edition of Nature this week, Duke's Jenny Tung led a study that combined sequencing, genotyping, and functional assays to take a peek at the evolution of a malaria resistance gene in wild primates. Screening about 200 yellow baboons from Amboseli National Park in Kenya, they tested for the presence of Hepatocystis kochi, a blood parasite related to Plasmodium. In 174 of these, they sequenced the region of DNA homologous to the human FY cis-regulatory region and found six SNPs in the baboon FY cis-regulatory region, genetic variation that is "associated with phenotypic variation in susceptibility to Hepatocystis," they say. They add that this is the "first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates."
In the current issue, a news feature profiles iPlant, a $50 million, five-year program funded by the NSF. While it was formed to tackle the big computational problems in plant science by setting up a new infrastructure for managing data, it's just begun to find its footing. Groups in the plant community now have about six "grand-challenge projects" that range from evolutionary genetics to the mathematical modeling of plant development, says the story.
Work out of Gary Ruvkun's lab at Harvard checked into the genetics behind why C. elegans mutants with increased longevity actually live longer. Studying gene expression changes, they found that in the mutants lower insulin-like signaling results in the "somatic misexpression" of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues, making these somatic cells appear more germ-like than somatic and thereby protecting them from genotoxic stress and aging.
Lynda Chin at Harvard's Dana-Farber Cancer Institute was senior author on a paper that followed up on GWAS data showing frequent 5p13 amplification in lung, ovarian, breast, and prostate cancer and melanoma. Using "integrative analysis of a genomic profile of the region," the team identified the Golgi protein, GOLPH3, as an amplification target and used gain- and loss-of-function experiments to validate GOLPH3 as an oncogene capable of affecting the response of cells to the cancer drug, rapamycin.
And, in Nature Genetics this week, James Lupski presents a DNA replication-based mechanism of fork stalling and template switching (FoSTeS) to explain complex rearrangements in a human dysmyelinating central nervous system disorder, and then makes it more general by including a microhomology-mediated break-induced replication (MMBIR) model. In this paper, he and his team show that human genomic rearrangements ranging in size from several megabases to a few hundred bases can be generated by FoSTeS/MMBIR, and that these variations can lead to duplicate or triplicate genes and even rearrangements of single exons.