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Yuqing He and colleagues show that Chalk5, a major quantitative trait locus for grain chalkiness in rice, encodes a vacuolar pyrophosphatase with H+ translocation activity. They find that elevated expression of Chalk5 disturbs the endomembrane trafficking system in developing seeds, leading to an accumulation of vesicle-like structures and increased chalkiness.
Gonçalo Abecasis, Chaolong Wang and colleagues report a new statistical method, implemented in a publicly available software program LASER, to estimate an individual's genetic ancestry directly from off-target sequence reads from targeted sequencing experiments, making use of a reference panel. Their simulations and testing on real data sets show accurate inference of worldwide continental ancestry with whole-genome shotgun coverage as low as 0.001× and of fine-scale ancestry within Europe with coverage as low as 0.1×.
Cristen Willer, Kristian Hveem and colleagues use an exome array to identify a coding variant in TM6SF2 that is associated with total cholesterol levels. They further show that transient overexpression of TM6SF2 or knockdown of Tm6sf2 in mice alters serum lipid profiles, implicating TM6SF2 as a causal regulator of lipid traits.
Nazneen Rahman, Katrina Tatton-Brown and colleagues identify de novo mutations in the DNA methyltransferase gene DNMT3A as the cause of a new overgrowth syndrome. Shared features of this syndrome include a distinctive facial appearance, intellectual disability and greater height.
Richard Thompson, Melissa Sambrotta and colleagues show that biallelic mutations in TJP2 cause severe cholestatic liver disease. Their findings suggest that loss of TJP2 protein disrupts the structural integrity of tight junctions in liver tissue, resulting in progressive liver damage.
Patrick H O'Farrell and colleagues show not only that deleterious variants are selected against but that complementing mutant mitochondria are selected at characteristic stable ratios.
Hong Xu and colleagues demonstrate reduced germline replication and selection against the transmission of mitochondria encoding a temperature-sensitive cytochrome c oxidase subunit.
Michelle Kelliher, Bradley Bernstein and colleagues identify T cell acute lymphoblastic leukemia cells that are resistant to γ-secretase inhibitor treatment and characterize the epigenetic mechanism of resistance.
David Altshuler and colleagues report genotyping or sequencing of ∼150,000 individuals from several population-based cohorts, identifying 12 rare protein-truncating variants in SLC30A8, encoding a pancreatic islet zinc transporter. Carriers of these rare protein-truncating variants in SLC30A8 show reduced risk of type 2 diabetes and reduced glucose levels.
Sanghyuk Lee, Young Hyeh Ko and colleagues report exome and transcriptome sequences for angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, and identify a recurrent somatic mutation in RHOA.
Community standards for data access, interoperability and metadata only make sense if data are creatively reused to further research. We are therefore inviting the submission of Analysis papers that reformat and integrate existing data sets to generate substantial novel insights into gene expression in cell differentiation transitions and different cell fates.
Sex chromosomes in mammals, birds, reptiles and fish represent many independent evolutionary events, but there is spectacular convergence and stunning parallels. A new study details the early stages of ZW differentiation and sex determination in a flatfish and the establishment of dosage compensation and sex reversal by epigenetic mechanisms including DNA methylation.
Cell fate regulation is a central component of maintaining tissue homeostasis, yet the mechanisms instructing cell division diversity in tissue-specific stem cells have not been well understood. A new study uncovers a central role for microtubule motor–regulating protein Lis1 in hematopoietic stem cell fate determination and in leukemogenesis.
Clear cell renal cell carcinoma (CCRCC) is characterized by mutation of the VHL gene and loss of a segment of chromosome 3. A new study using multi-region exome sequencing has identified substantial intratumoral heterogeneity within large primary CCRCCs, which has profound implications for understanding tumor evolution and for developing effective therapies.