In PLoS Genetics this week, researchers in New York, Florida, and Tennessee combined data on 483,399 SNPs from previously reported GWAS on late-onset Alzheimer's disease in order to identify novel genetic association signals. The team observed and replicated a novel statistically-significant association in the MTHFD1L gene, which is involved in the tetrahydrofolate synthesis pathway. "This finding is noteworthy, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways and as levels of homocysteine are a significant risk factor for LOAD development," the authors write.
Also in PLoS Genetics , researchers in Pennsylvania used genome-wide double-stranded RNA sequencing to reveal the functional significance of base-paired RNAs in Arabidopsis. The team used a combination of classical nuclease-based structure mapping techniques and high-throughput sequencing to interrogate all base-paired RNA in Arabidopsis thaliana, and identified about 200 new small RNA–producing substrates of RNA–dependent RNA polymerase 6. "Our comprehensive analysis of paired RNAs reveals conserved functionality within introns and both 5′ and 3′ untranslated regions (UTRs) of mRNAs, as well as a novel population of functional RNAs, many of which are the precursors of smRNAs," the authors write.
In PLoS One , researchers in Ohio report on cDNA microarray gene expression profiling of hedgehog signaling pathway inhibition of human colon cancer cells. The team employed a small molecule inhibitor of both GLI1 and GLI2, GANT61, in two human colon cancer cell lines, HT29 and GC3/c1. They then performed a cell cycle analysis which demonstrated accumulation of GANT61-treated cells at the G1/S boundary. "Novel genes involved in stress response, DNA damage response, DNA replication and DNA repair were identified following inhibition of HH signaling," the authors write.
And in PLoS Biology this week, researchers at Duke University show how a widespread chromosomal inversion polymorphism contributed to adaptation and speciation. Looking at replicated crosses between the pre-zygotically reproductively isolated annual and perennial ecotypes of the yellow monkeyflower, the researchers saw that alternative chromosomal inversion arrangements are associated with life-history divergence over thousands of kilometers across North America. "The inversion polymorphism affected adaptive flowering time divergence and other morphological traits in all replicated crosses between four pairs of annual and perennial populations," the authors write. "Our results demonstrate for the first time in nature the contribution of an inversion to adaptation, an annual/perennial life-history shift, and multiple reproductive isolating barriers." Our sister publication GenomeWeb Daily News has more on this study here.