Letters in 2016

Magnus Nordborg and colleagues report a genomic analysis of all 27 known species in the genus Arabidopsis. They find evidence for a complex speciation history that is not accurately reflected by a traditional bifurcating species tree and identify widespread shared polymorphisms between species.

Timothy Vyse, Yong Cui, Wanling Yang and colleagues report a meta-analysis of genome-wide association studies for systemic lupus erythematosus (SLE) including European and Chinese individuals. They identify ten new loci associated with SLE and find evidence for increased genetic risk of disease among individuals of non-European ancestry.

Li Yu, Ya-Ping Zhang, Chung-I Wu and colleagues report the de novo genome of the black snub-nosed monkey Rhinopithecus bieti and the genomic sequences of four other Rhinopithecus species, including three high-altitude and two lowland species. The species- and population-level genomic analyses as well as the transcriptomic analysis and functional assays find adaptive signatures associated with adaptation to high altitude.

Dominic Kwiatkowski and colleagues report a population genomic analysis of 228 clinical samples of Plasmodium vivax from 13 countries, with an emphasis on Southeast Asia. They analyze patterns of genetic structure within individual infections and find evidence for regional adaptation at the population level.

Jane Carlton, Daniel Neafsey and colleagues report a population genomics analysis of 182 Plasmodium vivax isolates from 11 countries. They find evidence of regional adaptation and signatures of selection at genes involved in antimalarial drug resistance.

Christian Gilissen, John Niederhuber and colleagues examine de novo mutations with parent-of-origin information from whole-genome sequencing datasets from 816 parent–offspring trios. They find maternal and paternal specific mutation signatures that are more prominent with increased age of the parent as well as clustered mutation signatures with no parental bias.

Patrick H O'Farrell and Hansong Ma simultaneously introduce mitochondrial genomes from distantly related strains or other species into Drosophila melanogaster, rate fly fitness and follow mitochondrial DNA transmission. They find evidence for selfish selection, where genomes with compromised function outcompete fully competent ones, and identify mitochondrial sequences responsible for the selfish behavior.

Satoshi Narumi, Tomonobu Hasegawa and colleagues describe a new adrenal hypoplasia syndrome termed MIRAGE that is caused by mutations in the endosome fusion facilitator SAMD9. They find that patients with these mutations have severe growth restriction phenotypes, and they observe adaptation by aneuploidy, where there is accompanying protective loss of mutation-carrying chromosome 7.

Amanda Spurdle, Ian Tomlinson, Douglas Easton and colleagues conduct a GWAS meta-analysis and identify five new risk loci for endometrial cancer. Functional studies show that one risk-associated SNP is located in an active chromatin region that interacts with the KLF5 promoter.

Xiaofeng Cao and colleagues report that the H3K27 demethylase REF6 binds directly to a specific DNA sequence through its Cys₂His₂ zinc-finger domains. They show that Arabidopsis thaliana mutants for REF6 exhibit defects in cotyledon separation, thereby linking sequence-specific H3K27me3 demethylation to organ boundary formation.

Yuhai Cui and colleagues report that the H3K27 demethylase REF6 targets genomic loci containing a specific DNA motif via its zinc-finger domains. They show that REF6 facilitates the recruitment of BRM and that deleting the DNA motif from a target gene in Arabidopsis makes it inaccessible to REF6.

Yu Chen and colleagues describe a new constitutively activating mutation in the G-protein-coupled receptor CYSLTR2 in patients with uveal melanoma lacking mutations in the G-protein-encoding genes GNAQ and GNA11. They find that expression of the mutant leads to increased expression of melanocyte-lineage signature genes and promotes tumorigenesis in vivo.

Wendy Bickmore, Madapura Pradeepa and colleagues identify a new class of active enhancers marked by histones with modifications on residues in the globular domain. They find that H3K64ac and H3K122ac are markers for active promoters and enhancers in embryonic stem cells and human cancer cell lines.

Meredith Yeager, Stephen Chanock and colleagues analyze mosaic loss of the Y chromosome in three prospective cohorts and observe association with age and smoking but not with cancer survival. They also identify common variation at TCL1A associated with increased risk of mosaic loss of the Y chromosome.

Douglas Epstein and colleagues use de novo motif analysis to identify sequence motifs and cognate transcription factors for brain enhancers of Shh active in the zona limitans intrathalamica (zli). They find new zli enhancers in mice and a functional equivalent in hemichordates, indicating an ancient origin of these sequence elements.

Chiea Chuen Khor, Tin Aung and colleagues report the results of a large genome-wide association study of primary angle closure glaucoma. They identify five new susceptibility loci and provide insights into disease pathogenesis.

Hiroyuki Mano and colleagues report fusions involving DUX4 in 16.4% of Ph-negative adolescent and young adult acute lymphoblastic leukemia (AYA-ALL) cases. Transplantation assays in mice support an oncogenic role for the DUX4-IGH fusion gene, which expresses DUX4 protein with an aberrant C terminus at high levels in patients with AYA-ALL.

Elise Robinson, Mark Daly and colleagues present an analysis of genetic data from autism spectrum disorder (ASD) and population-based studies and find evidence for genetic correlations between ASDs and typical variation in social behavior and communication traits. These results may inform genetic models of ASDs and other neuropsychiatric disorders.

James Collins and colleagues explore the role of the bacterial epigenome in antibiotic stress survival. They find that Escherichia coli survival under antibiotic pressure is strongly compromised in the absence of adenine methylation at GATC sites, suggesting that targeting adenine methylation might be a viable approach to enhance antibiotic activity.

Friedhelm Hildebrandt and colleagues identify mutations in NUP93, NUP205 or XPO5 in patients with steroid-resistant nephrotic syndrome. They show that NUP93 and XPO5 interact with SMAD4 and that NUP93 mutations interfere with BMP7-SMAD4 signaling in podocytes.