Research articles

Tatsuhiro Shibata, David Wheeler, Hiroyuki Aburatani and colleagues report the genomic, exomic and oncoviral sequencing of hundreds of liver cancers from the United States and Japan. The authors analyzed mutation patterns and identified signatures unique to the Asian cases.

Holger Lerche, Camila Esguerra and colleagues report the identification of inactivating mutations in STX1B in individuals with various seizure-related disorders, including febrile seizures and epilepsy. Functional studies indicate that STX1B acts in the presynaptic release machinery.

Peter Sorger, Mohammed AlQuraishi and colleagues present a statistical framework for integrating biophysical and genomic data to predict the consequences of cancer-related mutations on protein-protein interactions. They apply their framework to the SH2 phosphoprotein network using publicly available data from The Cancer Genome Atlas.

Zachary Lippman and colleagues report the recovery in tomato of novel, chemically induced alleles in the SFT (florigen) gene and a newly identified suppressor of the SELF PRUNING gene. These alleles, in combination with previous florigen pathway mutations, allow for the quantitative fine-tuning of fruit yield, which may be applicable to other crop species.

Ming Li, Ruiqiang Li and colleagues report the whole-genome sequencing of a male golden snub-nosed monkey, Rhinopithecus roxellana, as well as its relatives Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri. Their analysis provides insights into primate evolution and adaptation to a diet consisting primarily of leaves and seeds.

Levi Garraway and colleagues report the identification of somatic mutations of RNF43, which encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling, in over 18% of colorectal adenocarcinomas and endometrial carcinomas.

Bjarke Feenstra and colleagues identify common variants at six loci associated with general or MMR vaccine–related febrile seizures. The two loci specifically associated with MMR-related febrile seizures harbor the interferon-stimulated gene IFI44L and the measles virus receptor gene CD46.

Andrew Jackson, Peter Nürnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction.

David Jaffe and colleagues report a new algorithm, DISCOVAR, for variant calling and de novo genome assembly. They test the algorithm on a new reference variant call set and demonstrate improved variant calling, particularly in challenging regions of the genome.

Frank Steemers and colleagues report a new method for genome-wide haplotyping based on contiguity-preserving transposition and combinatorial indexing. They apply this method to assemble over 95% of the heterozygous variants in a human genome into long, accurate haplotype blocks.

Evan Eichler and colleagues present a detailed characterization of the chromosome 15q13.3 microdeletion region. They identify complex structural polymorphisms and find that the rearrangement breakpoints cluster in palindromic GOLGA8 core duplicons, providing evidence that this repeat and its palindromic architecture underlie the evolutionary and disease-related instability of this region.

Chetan Bettegowda, Bert Vogelstein and colleagues identify somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors from individuals with and without neurofibromatosis. SUZ12 encodes a chromatin-modifying protein and is located adjacent to the NF1 gene on chromosome 17q11. The data support a 'three-hit' model of tumor suppression.

Sanwen Huang and colleagues report a comprehensive analysis of genetic variation in tomato based on the genome sequencing of 360 distinct accessions. The work provides insights into the history of tomato domestication and represents a rich resource for studying the genetic basis of trait variation in this important crop plant.

Ali Gharavi and colleagues report a genome-wide association analysis of IgA nephropathy in over 20,000 individuals of European and East Asian ancestry. They identify genome-wide significant signals at three new loci near VAV3, CARD9 and ITGAM-ITGAX and correlations between genetic risk and pathogen diversity.

Gregor Andelfinger and colleagues identify mutations in SGOL1 that cause a novel cohesinopathy characterized by chronic atrial and intestinal dysrhythmia, termed CAID syndrome. SGOL1 encodes a component of the cohesin complex, suggesting that cardiac and gut rhythm are regulated by this complex.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Fernando González-Candelas and colleagues report the whole-genome sequencing of 69 Legionella pneumophila strains linked to recurrent outbreaks in Alcoy, Spain, over the course of 11 years. They characterize the evolution and epidemiology of this environmental pathogen.

William Lee and colleagues present a systematic analysis of noncoding somatic mutations in 863 tumor samples representing over 20 cancer types. They identify new mutation hotspots as well as genes with frequent mutations in their promoter regions, including WDR74 and SDHD.

Kristijan Ramadan and colleagues report the identification of three individuals from two families with biallelic inactivating mutations in SPRTN causing early onset hepatocellular carcinoma and defects in the DNA replication stress response. Functional studies confirmed critical roles for SPRTN in G2/M checkpoint response and DNA replication.

James Cerhan and colleagues report genome-wide association and meta-analysis studies to identify genetic susceptibility loci for diffuse large B cell lymphoma. They identify four loci that influence genetic susceptibility to this B cell malignancy.