Volume 52 Issue 12, December 2020

Maintaining ignorance to self-nucleic acids can prevent inflammatory diseases such as Aicardi–Goutières syndrome (AGS). A new study finds that mutations in LSM11 and RNU7-1, which encode components of the histone messenger RNA–preprocessing complex, cause AGS by loosening the binding of cyclic GMP–AMP synthase (cGAS) to nucleosomes, thus enabling cGAS activation and induction of type I interferons.

Recent progress relating to the catalytic and non-catalytic functions of histone modifying complexes warrants a fresh look at the role of histone modifications and the “histone code” model.

dACE2 is a newly identified isoform of ACE2 that is unable to bind the SARS-CoV-2 spike protein. Truncated dACE2, but not full-length ACE2, is induced by interferons and viruses, thus suggesting that such conditions are unlikely to increase cellular entry of SARS-CoV-2.

A truncated angiotensin-converting enzyme 2 (ACE2) isoform that lacks domains required for severe acute respiratory syndrome coronavirus 2 binding exhibits tissue-specific expression patterns and is responsive to interferon stimulation, in contrast to full-length ACE2, which is unresponsive to interferons.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Enhancer variants associated with red blood cell traits alter signaling transcription factor motifs, leading to changes in expression of genes that are upregulated during erythroid differentiation.

A resource of cell-type-specific IMPACT regulatory annotations improves the trans-ancestry portability of polygenic risk scores by prioritizing variants enriched for trait heritability.

PolyFun is a computationally scalable framework for functionally informed fine-mapping that makes full use of genome-wide data. It prioritizes more variants than previous methods when applied to 49 complex traits from UK Biobank.

Mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA–processing complex, cause an autoinflammatory syndrome due to enhanced interferon signaling mediated by the cGAS–STING pathway, showing an essential role for nuclear histones in suppressing the immunogenicity of self-DNA.

Harmonized analysis of 1,048 melanomas shows different global genomic properties among subtypes and identifies subtype-specific enrichment for secondary driver genes.

A BAH module in BAHCC1 recognizes H3K27me3 and is involved in gene silencing. BAHCC1 is highly expressed in acute leukemia cells and contributes to their proliferation.

MLL4 (KMT2D) loss of function, as found in Kabuki syndrome, affects the chromatin compartmentalization of Polycomb proteins and changes the nuclear architecture. Inhibition of ATR reestablishes mechanosignaling of mutant mesenchymal stem cells and their commitment to becoming chondrocytes.

Whole-genome sequencing of wheat populations from 25 subspecies within the genera Triticum and Aegilops provides insights into the role of evolutionary constraints in shaping the adaptive landscape of bread wheat.

Phased diploid genomes of the cultivated apple Malus domestica cv. Gala and its two major wild progenitors M. sieversii and M. sylvestris, as well as pan-genome analyses, provide insights into the genetic history of apple domestication.