Articles in 2016

Raul Rabadan, Antonio Iavarone, Gaetano Finocchiaro, Do-Hyun Nam and colleagues analyze longitudinal genomic and transcriptomic data from 114 patients with glioblastoma. They find that relapse-associated clones typically exist before diagnosis, that expression subtypes are not stable under therapy and that recurrence tumors harbor specific alterations in several genes, including LTBP4 and MGMT.

Han-Xiang Deng and colleagues identify TMEM230 mutations in Lewy body–confirmed Parkinson's disease. They also show evidence that disease-associated TMEM230 mutants impair synaptic vesicle trafficking in neurons.

Dongxin Lin, Chen Wu and colleagues identify a LINC00673 variant that associates with pancreatic cancer risk in Han Chinese cohorts. They show that the variant creates a target site for miR-1231 and that LINC00673 regulates PTPN11 degradation and leads to altered SRC–ERK and STAT1-dependent signaling.

Xuejun Zhang, Jun Wang, Liangdan Sun, Lennart Hammarström and colleagues sequence the MHC region in 20,635 Han Chinese individuals. Their Han-MHC database allows identification of new susceptibility loci for psoriasis and could serve as a tool for investigating the role of the MHC region in other complex diseases.

Andrea Superti-Furga, Ron Wevers, Clara van Karnebeek, Luisa Bonafé and colleagues identify mutations in NANS, which encodes the sialic acid synthase, in nine individuals with severe infantile-onset developmental delay and skeletal dysplasia. They describe abnormal metabolites accumulating because of deficient NANS enzyme activity and show that impaired sialic acid synthesis in zebrafish perturbs skeletal development, which can partially be rescued by supplementation with exogenous sialic acid.

David Jackson and colleagues identify FEA3, encoding an LRR-receptor-like protein in maize, which responds to signals from organ primordia to the stem cell niche to regulate stem cell proliferation, a function that is conserved in Arabidopsis. They find that weak alleles of fea3 enhance hybrid maize yield traits.

Sohrab Shah, Samuel Aparicio and colleagues analyze whole genomes and single cells from ovarian cancers in the peritoneal cavity to establish patterns of disease spread. They determine the clonal relationships between multiple tumor sites and characterize the migratory potential of genomically diverse clones.

John Wallingford and colleagues combine proteomics, in vivo imaging and genetic analyses to identify a new ciliopathy-associated protein module, which they call CPLANE. They show that CPLANE proteins, which include Fuzzy, Inturned and Wdpcp, interact with Jbts17 at basal bodies, where they act to recruit a specific subset of intraflagellar transport proteins.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

Philipp Simon, Massimo Iorizzo, Allen Van Deynze and colleagues report the high-quality assembly of the carrot genome, providing an important resource for crop improvement. They find a candidate gene that regulates carotenoid accumulation and gain further insights into asterid genome evolution, including characterization of two new polyploidization events.

Kari Stefansson and colleagues report discovery of 13 variants with large effects on non-HDL cholesterol, LDL cholesterol, HDL cholesterol or triglyceride lipid fractions. They further show that, among these lipid fractions, the non-HDL cholesterol genetic risk score associates most strongly with coronary disease and confers risk beyond that of LDL cholesterol and that, after accounting for non-HDL cholesterol, neither HDL cholesterol nor triglyceride genetic risk scores associate with coronary disease.

John Perry, Ken Ong and colleagues perform a genome-wide association study for reproductive ability, behavior and success to determine underlying genetic factors. They find 38 variants associated with age of first sexual intercourse and show that both physical and neurobehavioral traits influence the onset of reproductive activity.

Zhenglin Yang and colleagues use whole-exome sequencing to identify a rare variant in the FGD6 gene that is associated with the polypoidal choroidal vasculopathy subtype of wet age-related macular degeneration. They show that FGD6 regulates proangiogenic effects together with VEGF and that the mutation results in abnormal retinal vessel development.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes.

Alexander Pym, Ashlee Earl and colleagues use the whole-genome sequences from 498 strains of Mycobacterium tuberculosis to identify new genotypes conferring resistance to antitubercular drugs. They find that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, are associated with unexplained drug resistance and demonstrate that these mutations confer resistance to D-cycloserine.

Nadav Ahituv, Nicola Illing, Jeff Wall and colleagues sequence the genome of the bat Miniopterus natalensis and perform RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages. Their analyses identify genomic regions that may contribute to bat wing formation.

Bin Zhou and colleagues use genetic labeling in mice to show that endocardial cells of the sinus venosus substantially contribute to the liver vasculature, which thus shares a common developmental origin with coronary arteries. Inhibition of endocardial angiogenesis leads to reduced endocardial contribution to the liver vasculature and to defects in liver organogenesis.

Adrian Liston and colleagues use a transgenic mouse model to demonstrate that beta cell failure is a mechanistic commonality in type 1 and type 2 diabetes. They find that the changes in the molecular pathways identified as contributing to beta cell loss are paralleled in human islets from patients with type 2 diabetes.

David Ellinghaus and colleagues report a combined association analysis of five chronic inflammatory diseases. They identify 27 new associations and highlight disease-specific association patterns at shared susceptibility loci.