Volume 51 Issue 11, November 2019

A fundamental problem in rare-disease diagnostics is the lack of consensus as to which genes have sufficient evidence to attribute causation. To address this issue, we have created PanelApp (https://panelapp.genomicsengland.co.uk), a publicly available knowledge base of curated virtual gene panels.

A generic framework for providing participant information and implementing a tiered consent process for health genomic research in Africa can help to harness global health benefits from sharing and meta-analysis of African genomic data while simultaneously respecting and upholding the autonomy and individual choices of African research participants.

Two genetic studies uncover how domestication changed fruit quality traits in melon and watermelon. The studies combine population genomic and quantitative genetic tools to study crop evolution and provide breeders with comprehensive variation maps.

Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

Genome-wide analyses identify variants near HDAC9 associated with abdominal aortic calcification and other cardiovascular phenotypes. Functional work shows that HDAC9 promotes an osteogenic vascular smooth muscle cell phenotype, enhancing calcification and reducing contractility.

Cytokine-induced regulatory changes in human pancreatic islets illustrate the β-cell chromatin dynamics in response to a proinflammatory environment and implicate a role for islet enhancers in type 1 diabetes.

The rare loss-of-function allele p.Arg138* in SLC30A8 (encoding ZnT8) mediates protection against type 2 diabetes (T2D) through promoting better insulin secretion and enhanced glucose responsiveness, suggesting ZnT8 as a target for T2D treatment.

A comprehensive map of genomic variation in melon derived from resequencing of 1,175 accessions sheds light on the population structure and domestication history of melon and agronomic traits for melon breeding.

An improved watermelon reference genome and whole-genome resequencing of 414 cultivated and wild accessions provide insights into fruit quality traits and dessert watermelon evolution.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Genome-wide analyses in 19,629 individuals identify 365 independent variants associated with brain volumetric phenotypes. The study provides insight into the overlapping genetic architecture of brain volume measures and cognitive and mental health traits.

The authors explore the impact of nonsense-mediated mRNA decay (NMD) on human genetic disease and cancer immunotherapy by applying the rules of NMD across the genome as a resource called NMDetective.

Analysis of whole-genome sequencing and expression data for 17 tissues identifies short tandem repeats whose repeat number is associated with gene expression (eSTRs). Specific eSTRs are implicated in different complex traits through colocalization analysis with known genome-wide association study signals.