In a paper published online in advance in Nature this week, investigators at the Wellcome Trust Genome Campus and elsewhere report their creation of a "high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles," with which to interrogate mouse gene functions. To date, the team has produced more than 12,000 vectors and 9,000 conditional, targeted alleles in "highly germline-competent C57BL/6N embryonic stem cells," it writes. The authors add that the "high-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome." Our sister publication GenomeWeb Daily News has more on this study.
In another Nature advance online publication, the University of Rochester's John Karijolich and Yi-Tao Yu show that the conversion of uridine into pseudouridine — or pseudouridylation — of nonsense codons "suppresses translation termination both in vitro and in vivo." Further, Karijolich and Yu suggest that "targeted pseudouridylation represents a novel approach for promoting nonsense suppression in vivo," and that RNA modification "may offer a new way to expand the genetic code."
Over in Nature Genetics, members of the 1,000 Genomes Project this week present a comparative analysis of "male and female germline mutation rates from the complete genome sequences of two parent-offspring trios." In one family, the team was surprised to find that 92 percent of germline de novo mutations were from the paternal germline, while in another family, 64 percent were from the maternal germline. "These observations suggest considerable variation in mutation rates within and between families," the authors write. GenomeWeb Daily News has more on this study as well.
And in Nature Structural & Molecular Biology this week, investigators at the UK's Medical Research Council Laboratory of Molecular Biology and John Radcliffe Hospital show that the "cooperation of the ATRX [protein's] ADD domain and HP1 in chromatin recruitment results in a tri-partite interaction that may span neighboring nucleosomes and illustrates how the histone code is interpreted by a combination of multivalent effector-chromatin interactions." While mutations in the gene encoding ATRX cause a mental retardation syndrome, the authors write, the ADD domain of the wild-type protein product, "in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3" — which, they add, is required for the localization of ATRX to heterochromatin.