Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
Researchers from the University of Helsinki and the Karolinska Institute describe the driver mutations and potential biomarkers they detected in various subtypes of uterine leiomyoma, benign tumors that are better known as fibroids. The team did targeted gene and/or whole-genome sequencing on 94 leiomyomas and 60 matched myometrium control samples collected from women undergoing hysterectomies at Helsinki University Hospital. Together with array-based gene expression profiles, mutation patterns in the samples made it possible to define leiomyoma subtypes with a range of expression signatures and driver mutations. The study's authors say the work "emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well" and argue in favor of follow-up studies to gauge the utility of candidate biomarkers identified in the analysis.
A team from the US and Italy characterize a vitiligo risk variant that falls downstream of the human leukocyte antigen gene HLA-A, which codes for a major histocompatibility complex receptor protein. Following from a prior association study, the researchers set out to track down a causal variant in the vicinity of HLA-A. Using genotyping data thousands of individuals with or without vitiligo, together with RT-PCR assays, gene expression experiments, and other approaches, the investigators narrowed in on a vitiligo-related gain-of-function mutation affecting an apparent transcriptional enhancer that bumps up HLA-A expression in individuals with the risky hapotype.
Finally, American and British researchers report on small RNAs that shuttle between Arabidopsis thaliana shoots and root contribute to RNA-directed DNA methylation at thousands of sites across the plant's genome in root tissue. Using methylC sequencing, RNA sequencing, and two-way grafts of plants from several genotypes, the team looked at how DNA methylation corresponded to small RNA representations in the plants. The analysis indicated that small RNAs impact genome-wide DNA methylation patterns in the root — particularly within gene-rich parts of the genome containing endogenous transposable element superfamilies.