UPDATE (July 22, 2011): This paper has been retracted by its authors:
In an advance, online publication of Science this week, Boston University's Paola Sebastiani and her colleagues report 150 SNPs associated with "exceptional longevity," which they elucidated in a genome-wide association study of 1,055 centenarians and 1,267 controls — "spouses of centenarian offspring or children of parents who died at the mean age of 73 years." The team also found that, using these SNPs, they could predict exceptional longevity with 77 percent accuracy in an independent cohort. "Further in silico analysis revealed that 90 percent of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes," Sebastiani et al. write, adding that these genetic signatures correlate with variations in the prevalence — and age-of-onset — of age-related diseases.
A BGI-led team reports that their sequencing project of 50 human exomes shows residents of the Tibetan Plateau have adapted to living at extreme altitudes. The transcription factor EPAS1, which is involved in response to hypoxia, showed the "strongest signal of natural selection," the authors write. Their paper appears alongside that of an international team, which examined the "genetic evidence for high-altitude adaption" among Tibetans — published online in advance — in this week's issue of Science.
Petra Hajkova and colleagues this week show that "genome-wide reprogramming in the mouse germ line entails the base excision repair pathway." Specifically, the authors report that DNA demethylation in mouse primordial germ cells is tied to the occurrence of single-stranded DNA breaks and BER pathway activation. "We demonstrate that DNA repair through BER represents a core component of genome-wide DNA demethylation in vivo and provides a mechanistic link to the extensive chromatin remodeling in developing PGCs," the authors conclude.
A trio of researchers at Brandeis University writes in Science this week that in their examinations of "the fidelity of DNA synthesis during double-strand break repair in Saccharomyces cerevisiae," they've demonstrated that "the mutation rate increases up to 1,400 times over spontaneous events," and that microhomology-mediated template switches are "especially prominent." For the most part, the authors write, recombination-induced mutations are independent of mismatch repair. Wade Hicks et al. suggest that "increased DSB frequencies in oncogene-activated mammalian cells may also increase the probability of acquiring mutations required for transition to a cancerous state."