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DNA methylation is an epigenetic mark stably directing gene expression throughout development. A new study uncovers a role for the DNA methyltransferase Dnmt3a in silencing self-renewal genes in hematopoietic stem cells (HSCs) to permit efficient hematopoietic differentiation.
Recent studies, including two in this issue, report heterozygous missense mutations in the U2AF1 and SF3B1 genes that encode spliceosome subunits. U2AF1 is frequently mutated in myeloid hematopoietic malignancies, especially in myelodysplastic syndrome (MDS), and SF3B1 is frequently mutated in both MDS and chronic lymphocytic leukemia (CLL).
Every instance of a variant in the human genome causing or correlated with a trait deserves to be databased and analyzed. As a consequence of rapidly evolving technology and strategies, more of the mutational spectrum of human disease is now accessible to research. Advised by our referees' progressively higher standards, we continue to select the most informative and useful results.
A new study reports the development of the 'morbidostat', a device that allows for continuous culture of bacteria under a constant drug selection pressure using computer feedback control of antibiotic concentration. This device, together with bacterial whole-genome sequencing, allowed the authors to follow the evolution of resistance-conferring mutations in Escherichia coli populations in real time, providing support for deterministic evolution of resistance in some situations.
Jiahao Sha, Xinru Wang, Hongbing Shen and colleagues report a genome-wide association study of non-obstructive azoospermia in Chinese men. They identify common variants near three genes (PRMT6, PEX10 and SOX5) associated with this form of male infertility.
Lavinia Paternoster and colleagues report a meta-analysis of genome-wide association studies of atopic dermatitis. They report three newly identified associated loci near OVOL1 and ACTL9 and in KIF3A.
Rosa Rademakers and colleagues show that mutations in CSF1R cause hereditary diffuse leukoencephalopathy with spheroids, a central nervous system white-matter disease with variable clinical presentations that include personality and behavioral changes, dementia, depression, parkinsonism and seizures.
Nicholas Hayward and colleagues sequenced eight metastatic melanoma exomes and identified frequent somatic mutations in two MAP kinase family genes, MAP3K5 and MAP3K9. Mutation in MAP3K9 may confer resistance to temozolomide, a common chemotherapeutic drug.
Xue-Qing Yu, Jian-Jun Liu and colleagues report results of a genome-wide association study of IgA nephropathy in Han Chinese. They identify two new susceptibility loci at 8p23 and 17p13 and replicate previously reported signals in the MHC region and at 22q12.
Sergey Nikolaev, Stylianos Antonarakis and colleagues report exome sequencing of seven melanoma cell lines and matched germline cells. They identify recurring somatic mutations in MAP2K1 and MAP2K2 occurring at an overall frequency of 8%.
Roy Kishony and colleagues develop a device for the continuous culture of bacterial populations under constant antibiotic selection pressure. They use this morbidostat, together with whole-genome sequencing of E. coli strains, to follow evolutionary paths leading to high levels of resistance to three individual drugs.
Dirk Schübeler, Michael Stadler and colleagues show that the c-Jun NH2-terminal kinase (JNK) binds directly to active promoters during the differentiation of stem cells to neurons and targets histone H3 serine 10 for phosphorylation.
Sebastien Gagneux and colleagues identify a set of compensatory mutations in the RNA polymerase of rifampicin-resistant M. tuberculosis by comparing the whole-genome sequences of ten paired clinical isolates and strains evolved in vitro. These mutations are associated with high competitive fitness in vitro and occur with increased clinical frequency in affected populations with a high burden of drug-resistant tuberculosis.