Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor (Oxtr) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species (n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research

Rights and responsibilities of individuals participating in medical research

Current geophysical knowledge of the planet Mercury is based upon observations from ground-based astronomy and flybys of the Mariner 10 spacecraft, along with theoretical and computational studies. Mercury has the highest uncompressed density of the terrestrial planets and by implication has a metallic core with a radius approximately 75% of the planetary radius. Mercury’s spin rate is stably locked at 1.5 times the orbital mean motion. Capture into this state is the natural result of tidal evolution if this is the only dissipative process affecting the spin, but the capture probability is enhanced if Mercury’s core were molten at the time of capture. The discovery of Mercury’s magnetic field by Mariner 10 suggests the possibility that the core is partially molten to the present, a result that is surprising given the planet’s size and a surface crater density indicative of early cessation of significant volcanic activity. A present-day liquid outer core within Mercury would require either a core sulfur content of at least several weight percent or an unusual history of heat loss from the planet’s core and silicate fraction. A crustal remanent contribution to Mercury’s observed magnetic field cannot be ruled out on the basis of current knowledge. Measurements from the MESSENGER orbiter, in combination with continued ground-based observations, hold the promise of setting on a firmer basis our understanding of the structure and evolution of Mercury’s interior and the relationship of that evolution to the planet’s geological history