Volume 48 Issue 7, July 2016

Stem cell regulation is critical to the development of all multicellular organisms; in plants, stem cell niches reside in meristems. Two newly identified plant genes establish a novel signaling feedback from the incipient leaf primordia back to the meristem that is required to regulate stem cell proliferation.

A new genetic disorder might be treatable through consumption of a simple sugar, but the relative contributions of endogenous and dietary sources are mostly unknown. It's time to change that.

A new analysis has identified hundreds of loci that are associated with multiple traits or diseases by comparing genome-wide association study (GWAS) data for 42 complex traits. The study uses the power of GWAS to provide evidence of pairs of traits with a likely causal relationship.

Joseph Pickrell and colleagues analyze genome-wide association data for 42 human phenotypes or diseases and identify several hundred loci influencing multiple traits. They also find several traits with overlapping genetic architectures as well as pairs of traits showing evidence of a causal relationship.

Jacob Gratten and colleagues use population genetic models to assess the genetic relationship between paternal age and risk of psychiatric illness. These models suggest that age-related mutations are unlikely to explain much of the increased risk of psychiatric disorders in children of older fathers.

Shirley Liu, Jun Liu and colleagues present a computational method to infer the CDR3 sequences of tumor-infiltrating T cells from RNA-seq data. They apply the method to 9,142 samples across 29 cancer types and show that it can be used to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.

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.

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.

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.

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.

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.

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.

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.

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.

Soumya Raychaudhuri, Buhm Han and colleagues present a statistical method to distinguish whether shared genetic risk variants among complex traits are driven by whole-group pleiotropy or a subset of individuals who constitute a genetically heterogeneous subgroup. They use the method to examine genetic sharing among autoimmune diseases and between major depressive disorder and schizophrenia and find that most genetic sharing cannot be explained by subgroup heterogeneity but that, in contrast, seronegative rheumatoid arthritis is a heterogeneous condition.

Po-Ru Loh, Pier Francesco Palamara and Alkes Price develop a new long-range phasing method, Eagle, that harnesses long, shared identical-by-descent tracts and can be applied to large outbred populations. They use Eagle to phase samples from the UK Biobank and find that it is faster and has better accuracy than existing methods.

Jonathan Marchini and colleagues develop a new method for haplotype phasing, SHAPEIT3, capable of handling large data sets from biobanks containing >100,000 genotyped samples. They find that their method is fast and accurate, with a low switch error rate, and can be scaled to data sets from increasingly larger cohorts.