Articles in 2016

Housheng Hansen He and colleagues perform an integrated analysis and identify 45 candidate long noncoding RNAs (lncRNAs) associated with prostate cancer risk. They further show that a prostate cancer risk allele in the 8q24 region results in upregulation of the lncRNA PCAT1, which promotes prostate cancer cell proliferation and tumor growth.

Nicholas Navin and colleagues use highly multiplexed single-nucleus sequencing to investigate DNA copy number evolution in patients with triple-negative breast cancer. Their data suggest that most copy number alterations are acquired at the earliest stages of tumor evolution in short punctuated bursts, followed by stable clonal expansions that form the tumor mass.

Xiaowu Wang, Jian Wu, Guusje Bonnema and colleagues report resequencing and subgenome selection analysis of 199 Brassica rapa and 119 Brassica oleracea accessions representing diverse morphotypes. They identify 4 subgenome loci with evidence of parallel selection among subgenomes and 15 subgenome loci with evidence of parallel selection between species.

Feng Qin and colleagues perform a genome-wide association study for drought tolerance in maize seedlings and find 42 candidate genes. They characterize a promoter insertion in the ZmVPP1 gene containing MYB-binding sites, which enables the drought-inducible expression of ZmVPP1, leading to drought tolerance, a phenotype confirmed through transgenic experiments.

Howard Chang, Ravindra Majeti and colleagues define the chromatin accessibility and transcriptional landscapes in 13 human primary blood cell types and in acute myeloid leukemia cells. They identify potential regulators governing hematopoietic differentiation and genetic elements linked to regulatory evolution in cancer cells.

Yongfeng Shang and colleagues report that the pioneering factor FOXA1 associates with DNA repair complexes and regulates DNA demethylation at its genomic targets in a DNA polymerase β–dependent manner. They show that FOXA1-associated DNA demethylation is coupled with genomic targeting of estrogen receptor α and estrogen responsiveness in a breast cancer cell line.

Ashley Winslow, Roy Perlis, David Hinds and colleagues report the identification of 15 genetic loci associated with risk of major depressive disorder in individuals of European descent. They find that several loci are also associated with risk of other psychiatric traits, including schizophrenia and neuroticism.

Jonathan Pritchard, Christopher Garcia and colleagues examine associations between different T cell receptor V genes and MHC alleles by eQTL mapping. They find that there are strong associations between MHC variation and T cell receptor gene usage and map these signals to specific MHC amino acids, many of which physically interact with germline-encoded amino acids on the T cell receptor.

Margaret Goodell, Wei Li and colleagues use double-knockout mice for Dnmt3a and Tet2 to model leukemia development. Through epigenetic and transcriptional analyses, they show that loss of DNMT3A and TET2 upregulates lineage-specific transcription factors such as KLF1 in hematopoietic stem cells and accelerates malignancy.

Robbie Waugh, Nils Stein, Gary Muehlbauer and colleagues report the exome sequencing of 267 landraces and wild accessions of barley from diverse regions to study adaptations to different agricultural environments. They observe correlations of days to heading and height with environment and find that variation in flowering-associated genes has strong geographical structuring.

Nathan Pankratz, Santhi Ganesh and colleagues use exome chip data to identify rare and common variants influencing blood cell traits. They report associations at several loci, including a rare missense variant in S1PR4 associated with circulating neutrophil counts, and present functional studies supporting a role for S1PR4 in neutrophil recruitment and resolution in response to tissue injury.

Sharon Kolk, Tjitske Kleefstra and colleagues identify loss-of-function mutations in SIN3A in individuals with intellectual disability and other clinical features. They further show that knockdown of Sin3a in developing mouse brain results in reduced cortical neurogenesis, altered neuronal identity and aberrant cortical projections, identifying this MeCP2-interacting protein as a key regulator of cortical development.

Jonathan Flint, Richard Mott and colleagues employ low-coverage (0.15×) sequencing and their new imputation method STITCH to perform genome-wide association analysis for complex traits in an outbred mouse population. They find >250 QTLs for 92 phenotypes and obtain gene-level mapping resolution for around 20% of the loci.

Lothar Hennighausen and colleagues identify 440 mammary-specific super-enhancers in mouse and focus on the STAT5-regulated Wap gene. Genetic dissection of the Wap super-enhancer suggests an internal hierarchy, as mutations in one of the constituent enhancers incapacitate the entire regulatory region.

Douglas Higgs and colleagues functionally test the α-globin super-enhancer in mice by genetically deleting its constituent enhancers. They find that the individual regulatory elements seem to act independently and in an additive way with respect to hematological phenotype, gene expression, and chromatin structure and conformation.

Abraham Palmer and colleagues use genotyping by sequencing to perform genome-wide association studies on CFW mice for behavioral, physiological and gene expression traits. They find many QTLs and incorporate expression QTL analysis to prioritize specific genes at loci of interest that underlie different complex traits.

Helga Salvesen, Rameen Beroukhim, Scott Carter and colleagues study the evolutionary landscape of endometrial cancer by performing whole-exome sequencing of complex atypical hyperplasias, primary tumors and metastases. They identify recurrent alterations in primary tumors and suggest that driver events are generally shared by primary and metastatic tumors.

Makoto Matsuoka and colleagues use a whole-genome sequencing-based approach to perform genome-wide association analysis for important agronomic traits in rice. Using phenotypically diverse rice with low interrelationships, they rapidly identify novel genes associated with heading date, plant height and panicle number per plant, validating candidates with transgenic experiments.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

David Page and colleagues examine genes with bivalent chromatin modifications in male germ cells from five mammalian species and chicken. They find that the set of bivalently marked genes shared by all species represent evolutionarily ancient morphogenesis regulators, whereas genes showing lineage-specific bivalent marks act downstream of these core regulators.