University of Washington researcher Evan Eichler and colleagues from centers in the US, UK, and Europe describe an autism spectrum disorder subtype that involves mutations to CHD8, a gene coding for a chromodomain helicase DNA-binding protein. Based on past studies pointing to recurrent disruptions in CHD8 in individuals with ASD, the team set out to find additional cases with such alterations and determine what, if any, features they shared. Through targeted sequencing on more than 3,700 more children with ASD or developmental delay, the investigators identified 15 truncating mutations affecting CHD8 — alterations not found in almost 8,800 unaffected controls. ASD cases involving CHD8 mutations tended to involve shared facial features, gastrointestinal problems, and enlarged head size, researchers note, pointing to the presence of a CHD8-related ASD subtype.
A team from the University of California, San Diego, examined the three-dimensional interactions that occur between elements making up the immunoglobulin heavy-chain locus during in B lymphocyte development, using fluorescent tagging and a Tet-operator system to track the elements in pro-B cells. From the type of motion and interactions they identified in this system, the study's authors argue that "the viscoelastic nature of the nuclear environment causes coding elements and regulatory elements to bounce back and forth in a spring-like fashion until specific genomic interactions are established." Their results also provided a peek at the time it takes for DNA elements to encounter one another based on the three-dimensional structure of their topological domains.
Researchers from Harvard University, the Broad Institute, and elsewhere present a computational method for fleshing out gene interactions and biological pathways with the help of evolutionary information. The algorithm — known as "clustering by inferred models of evolution," or CLIME — considers evolutionary models inferred from phylogenetic, species, homology information, and gene level data, authors of the study explain. In their proof-of-principle analyses, the researchers applied this approach to 1,025 human gene sets and to proteomic data from several other organisms, identifying some evolutionarily conserved modules and co-evolving components not described previously.