Volume 50 Issue 12, December 2018

A new study identifies loss-of-function mutations in HAVCR2, which encodes TIM-3, in patients with a rare cutaneous T cell lymphoma associated with aberrant immunological activation. These mutations lead to loss of the TIM-3 immunological checkpoint, thus promoting inflammation and malignancy.

Mitochondrial variants are important to consider when analyzing the genetics of various metabolic or age-related diseases. These mtDNA variants can influence the penetrance of a phenotype or interact differentially with nuclear DNA variants.

This study finds germline loss-of-function mutations in HAVCR2, which encodes the immune modulator TIM-3, in individuals with subcutaneous panniculitis-like T cell lymphomas and hemophagocytic lymphohistiocytosis, a life-threatening inflammatory condition.

Retinoic acid and BMP4 signaling, together with p63, contribute to dynamic long-range chromatin interactions during keratinocyte differentiation. TP63 decreases chromatin accessibility and promotes H3K27me3 accumulation at enhancers.

In zebrafish, cilia-driven flow of cerebrospinal fluid transports adrenergic signals that induce urotensin neuropeptides in spinal cord neurons. In turn, these neuropeptides activate their receptor on nearby muscle fibers, straightening the body axis.

Analysis of 1,007 sibling pairs from 251 families identifies 878 de novo mutations shared by siblings at 448 sites. Recurrence probability based on parental somatic mosaicism, sibling sharing, parent of origin, mutation type and genomic position can range from 0.011% to 28.5%.

Genome-wide association meta-analysis of data sets from Iceland and the UK identifies 16 new risk loci for osteoarthritis, including missense variants in SMO, IL11, and COL11A1.

De novo assembly of 23 Aspergillus section Nigri and 6 Aspergillus niger genome sequences allows for inter- and intraspecies comparisons and prediction of secondary metabolite gene clusters.

Whole-genome sequencing of 175 Mongolians representing six tribes highlights population-specific genetic architecture and substantial gene flow among northern Eurasian populations, including derived alleles shared by Mongolians and Finns.

Targeted inactivation, restoration and overexpression of MALAT1 in multiple in vivo models demonstrate that the lncRNA MALAT1 suppresses breast cancer metastasis through binding and inactivation of the pro-metastatic transcription factor TEAD.

Eight genome-wide CRISPR screens identify genes required for substrate-specific phagocytosis. The study highlights roles for NHLRC2 in filopodia formation, very-long-chain fatty acids in substrate-specific phagocytosis and TM2D3 in uptake of amyloid-β aggregates.

This study presents a new latent causal variable (LCV) model that distinguishes between genetic correlation and causation. Applying LCV to genome-wide association summary statistics for 52 traits identified genetically causal effects for 59 pairs of traits.

A machine learning approach for refinement of somatic variant calls automates this process and reduces bias stemming from inter-reviewer variability.

Tri-C is a new 3C approach to identify concurrent chromatin interactions at individual alleles. The authors observe specific higher-order structures involving simultaneous interactions between multiple enhancers and promoters, called regulatory hubs.