Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids.

The engineered AAV-PHP.B family of adeno-associated virus efficiently delivers genes throughout the mouse central nervous system. To guide their application across disease models, and to inspire the development of translational gene therapy vectors for targeting neurological diseases in humans, we sought to elucidate the host factors responsible for the CNS tropism of the AAV-PHP.

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed.

A synthetic-diploid benchmark for accurate variant-calling evaluation.

Existing benchmark datasets for use in evaluating variant-calling accuracy are constructed from a consensus of known short-variant callers, and they are thus biased toward easy regions that are accessible by these algorithms. We derived a new benchmark dataset from the de novo PacBio assemblies of two fully homozygous human cell lines, which provides a relatively more accurate and less biased estimate of small-variant-calling error rates in a realistic context.

A simple and accurate craniofacial midsagittal plane definition.

Introduction: In this article, we aimed to establish an ideal definition for the craniofacial midsagittal plane (MSP) by first finding an optimal "plane of best fit" and then deriving a simple approximation for clinical use that is highly accurate.

Methods: For 60 adolescent patients, 3-dimensional coordinates of 8 central landmarks and 6 pairs of lateral landmarks were collected. Across all patients, the coplanarity of the central landmarks was compared with that of the midpoints of the lateral landmarks.

Ultra-rare disruptive and damaging mutations influence educational attainment in the general population.

Disruptive, damaging ultra-rare variants in highly constrained genes are enriched in individuals with neurodevelopmental disorders. In the general population, this class of variants was associated with a decrease in years of education (YOE). This effect was stronger among highly brain-expressed genes and explained more YOE variance than pathogenic copy number variation but less than common variants.