In an advance online article in this week's Nature, researchers at Northwestern University and their colleagues report that the disruption of the molecular clock-related transcription factors CLOCK and BMAL1 ultimately leads to hypoinsulinaemia and diabetes. They found that "pancreatic islets possess self-sustained circadian gene and protein oscillations of" both CLOCK and BMAL1, and that, in the context of Clock and Bmal1 mutant mice, glucose tolerance is impaired, insulin secretion is reduced, and "defects in size and proliferation of pancreatic islets that worsen with age." Further, Clock alterations lead to transcriptome-wide changes in islet gene expression, and "conditional ablation of the pancreatic clock causes diabetes mellitus due to defective β-cell function," the authors write.
Pier Paolo Pandolfi at Harvard Medical School and colleagues detail how the "coding-independent function of gene and pseudogene mRNAs regulates tumor biology." Pandolfi et al describe the functional relationship between mRNAs produced by the tumor suppressor gene PTEN and PTENPI, its pseudogene; they "show that the PTENP1 locus is selectively lost in human cancer," and that "the transcripts of protein-coding genes such as PTEN are biologically active." The authors suggest that their study reveals a non-coding function for mRNAs.
Meanwhile, in Nature Genetics, Stephen Chanock at the National Cancer Institute and his collaborators report their "set of tools to estimate the number of susceptibility loci and the distribution of their effect sizes for a trait on the basis of discoveries from existing genome-wide association studies." Using reported GWAS findings for a variety of traits, the team found that each is "likely to harbor additional loci within the spectrum of low-penetrance common variants," and "could explain at least 15-20 percent of the known heritability of these traits."
And in a news feature, Declan Butler discusses the results of a recent Nature survey that collected investigators' opinions on biomedical progress since the completion of the Human Genome Project. While respondents generally agreed that the potential for genomic medicine was "overblown" in the early genome era, 69 percent of them "were inspired by the genome to become a scientist or change their research direction," Butler writes. Butler adds that when the HGP "was envisioned, experts at the time 'predicted that it would take 15 years to generate the first sequences, and a century for biologists to understand it.'" National Human Genome Research Institute director Eric Green tells Nature: "I think they got that about right."