Researchers from Yale and Stanford argue the merits of recent work being done to annotate the non-coding regions of the human genome in Nature Reviews Genetics this week. Most of the genome consists of non-protein-coding DNA, the authors write, but recent progress has been made in annotating these regions through genome function experiments and comparative sequence analysis. The steps involved in functional genomics analysis include "turning the output of an experiment into a 'signal' at each base pair of the genome; smoothing this signal and segmenting it into small blocks of initial annotation; and then clustering these small blocks into larger derived annotations and networks," the researchers write.
In the advance online publication of Nature, researchers in California report on diverse somatic mutations and pathway alterations in human cancers. The team identified 2,576 somatic mutations across roughly 1,800 megabases of DNA, and found that mutation rates and sets of mutated genes varied across tumor types. "Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets," the authors write. "Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for Gα subunits in multiple cancer types." Their work, the researchers suggest, identifies several potential therapeutic targets.
Researchers in Massachusetts and Missouri suggest there is convergence of the evolution of the chicken and the human male chromosomes. A comparative comparison of the chicken Z and human X chromosomes show that each evolved independently from different portions of the ancestral genome, the authors write. But despite this, both chromosomes share features that set them apart from autosomes. "We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety," the researchers suggest. "More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females."
And also in Nature this week, an international team of researchers suggests that pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Mutations in LRRK2 cause familial and sporadic Parkinson's disease by an unknown mechanism, the authors write. But their work suggests that LRRK2 interacts with the microRNA pathway to regulate protein synthesis, antagonizing them, and leading to the overproduction of E2F1/DP, which is critical for LRRK2 pathogenesis. "Our results implicate deregulated synthesis of E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2 pathogenesis and suggest novel miRNA-based therapeutic strategies," the team says.