As our sister publication GenomeWeb Daily News reports, "a trio of papers from researchers associated with the ARRA Autism Sequencing Collaborative appearing in this week's issue of Nature outline exome sequencing studies that have identified de novo mutations associated with autism spectrum disorders."
Yale University School of Medicine's Stephan Sanders and his colleagues used a whole-exome sequencing approach on 928 individuals, including 200 phenotypically discordant sibling pairs, through which they found that "highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects."
The University of Washington School of Medicine's Brian O'Roak et al. report having sequenced the exomes of 209 parent-child trios exhibiting sporadic autism spectrum disorders and 50 unaffected siblings from some of those families, finding that "de novo point mutations are overwhelmingly paternal in origin and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD [autism spectrum disorders]."
Finally, a team led by Massachusetts General Hospital and Harvard Medical School's Benjamin Neale reports having sequenced the exomes of 175 ASD parent-child trios, finding that "fewer than half of the cases (46.3 [percent]) carry a missense or nonsense de novo variant," and that "the overall rate of mutation is only modestly higher than the expected rate." However, the team did find that "the proteins encoded by genes that harbored de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens."
On a different note over in Nature Methods, investigators at Stanford University and Cold Spring Harbor Laboratory in New York present a computational framework to identify RNA editing sites using transcriptome and deep-sequencing data from the same individual. "As compared with previous methods, our approach identified a large number of Alu and non-Alu RNA editing sites with high specificity," the authors write. "We also found that editing of non-Alu sites appears to be dependent on nearby edited Alu sites, possibly through the locally formed double-stranded RNA structure."