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This Week in Nature: Oct 11, 2018

In this week's Nature, University of Oxford researchers and colleagues publish two papers around the UK Biobank, one describing the open resource's full dataset and another that uses these data to study the brain's genetic architecture. In one report, the investigators describe the centralized analysis of the biobank's genetic data — which was obtained from roughly 500,000 individuals — including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. In the other paper, the scientists analyzed genetic and MRI brain scan data from 8,428 biobank participants, identifying a number genetic associations including genes involved in the transport and storage of iron, which can be involved in neurodegenerative disorders. The team also uncovers associations with genes that code for proteins implicated in synaptic plasticity and the repair of nerve fibers, or are related to depression, multiple sclerosis, or stroke. GenomeWeb has more on this here.

And in Nature Ecology & Evolution, an international team of scientists use genomic data from sharks to better understand the evolution of cartilaginous fishes, which diverged from jawed vertebrates around 450 million years ago and feature unique reproductive, longevity, and sensory traits. The researchers sequenced the genomes and transcriptomes of the brownbanded bamboo shark and cloudy catshark, and improved the genome assembly of the whale shark — the largest living fish — and compared the data to the genomes of other vertebrates. Among their findings are a slower rate of evolution among cartilaginous fish versus bony ones, as well as distinct gene repertories of light-sensitive opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. "We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor," the researchers write.

Meanwhile, in Nature Methods, a team of Novartis-funded scientists describe and validate a method — dubbed Gene Swap — to enable genome-scale pooled CRISPR-Cas9 screening in human primary cells. The approach is based on the finding that editing by lentivirally delivered, targeted guide RNAs (gRNAs) occurs efficiently when Cas9 is introduced in complex with non-targeting gRNA, the researchers explain. "We anticipate that this platform will be broadly applicable to other challenging cell types, and thus will enable discovery in previously inaccessible but biologically relevant human primary cell systems," they write.