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Showing: 1–25 of 50

  1. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

  2. The promise of discovering population-specific disease-associated genes in South Asia

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    Kumarasamy Thangaraj, David Reich and colleagues identify 81 South Asian groups descended from extreme founder events, including 14 with a census size of over 1 million people, thus providing an opportunity to test for and decrease the burden of recessive genetic diseases in these populations.

  3. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

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    Damian Smedley and colleagues report the phenotypic characterization of the first 3,328 genes by the International Mouse Phenotyping Consortium. They develop new mouse models based on genes known to be associated with human mendelian diseases and identify potential disease-associated genes with little or no previous functional annotation.

  4. Genetic variation, classification and 'race'

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    New genetic data has enabled scientists to re-examine the relationship between human genetic variation and 'race'. We review the results of genetic analyses that show that human genetic variation is geographically structured, in accord with historical patterns of gene flow and genetic drift. Analysis of many loci now yields reasonably accurate estimates of genetic similarity among individuals, rather than populations. Clustering of individuals is correlated with geographic origin or ancestry. These clusters are also correlated with some traditional concepts of race, but the correlations are imperfect because genetic variation tends to be distributed in a continuous, overlapping fashion among populations. Therefore, ancestry, or even race, may in some cases prove useful in the biomedical setting, but direct assessment of disease-related genetic variation will ultimately yield more accurate and beneficial information.

  5. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats

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    Christoph Plass and colleagues investigate the transcriptomic and epigenomic changes induced by treatment with inhibitors of DNMT and HDAC in cancer cell lines. They observe large numbers of treatment-induced non-annotated TSSs (TINATs) encoded in long-terminal repeats that are normally repressed in most cell types.

  6. The genome of woodland strawberry (Fragaria vesca) Open

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    The International Strawberry Sequencing Consortium reports the draft genome of the woodland strawberry (Fragaria vesca). The genome of this diploid species should serve as a reference genome for the Fragaria genus, as the cultivated strawberry (Fragaria × ananassa) is an octoploid where F. vesca is predicted to be a subgenome donor.

  7. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia

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    Charles Mullighan, Stephen Hunger, Jinghui Zhang and colleagues report a genomic analysis of 264 pediatric and young adult T-lineage acute lymphoblastic leukemia (T-ALL) samples. They identify 106 candidate driver genes, 53 of which have not been described previously in pediatric T-ALL, as well as associations between mutations and disease stage or subtype.

  8. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

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    Danielle Posthuma and colleagues perform a large meta-analysis for intelligence and determine genetic overlap with several neuropsychiatric and metabolic traits. They find 15 new significant loci and implicate 40 new genes, most of which are predominantly expressed in the brain.

  9. Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease

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    Sekar Kathiresan and colleagues perform a genome-wide association test for coronary artery disease (CAD) using data from the UK Biobank. They identify 15 new loci and perform phenome-wide association scanning, implicating insulin resistance pathways and transendothelial migration of leukocytes in CAD.

  10. Genotype–covariate interaction effects and the heritability of adult body mass index

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    Matthew Robinson, Peter Visscher and colleagues use phenotypic data on 172,000 sibling pairs and phenotypic and SNP data on 150,832 unrelated individuals to estimate the heritability of body mass index across a range of experimental designs. They conclude that substantially larger sample sizes across ages and lifestyle factors will be required to understand the full genetic architecture of this trait.

  11. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain

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    Schahram Akbarian and colleagues report that mutation of the gene encoding the SETDB1 (KMT1E) histone methyltransferase in mouse neurons leads to dissolution of chromosome conformations and a topologically associated domain at the clustered protocadherin locus. They show that SETDB1 prevents excess CTCF binding and is important for maintaining developmentally important higher-order chromatin organization.

  12. Genome-wide characterization of mammalian promoters with distal enhancer functions

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    Salvatore Spicuglia and colleagues use a high-throughput reporter assay to identify a set of mammalian promoters, termed Epromoters, that display enhancer activity and have distinct genomic and epigenomic features. Through CRISPR–Cas9 gene editing experiments, they show that Epromoters are involved in long-range gene regulation in cis.

  13. Association analyses based on false discovery rate implicate new loci for coronary artery disease

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    Hugh Watkins and colleagues meta-analyze data from the UK Biobank along with recent genome-wide association studies for coronary artery disease. They identify 13 new loci that were genome-wide significant and 243 loci at a 5% false discovery rate.

  14. High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development Open

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    Etienne Bucher and colleagues use a combination of short- and long-read sequencing, along with optical mapping technologies, to produce the high-quality de novo assembly of the apple genome. They identify a new repetitive retrotransposon sequence and analyze DNA methylation data in relation to important agronomic traits.

  15. Synchronized DNA cycling across a bacterial population

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    Jeff Hasty and colleagues use an endonuclease from S. cerevisiae along with quorum sensing from A. fischeri to produce sustained cycling of DNA plasmid concentration across a colony of E. coli cells. This copy number modulation system enables dynamic regulation of gene circuit elements without the need for specially engineered promoters.

  16. Ancient selection for derived alleles at a GDF5 enhancer influencing human growth and osteoarthritis risk

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    Terence Capellini, David Kingsley and colleagues use transgenic mice to show that a Gdf5 enhancer (termed GROW1) is required for normal bone length. They suggest that a common variant at the human GROW1 enhancer was under selection in human populations and also contributes to arthritis susceptibility.

  17. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution

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    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.

  18. Promoting transcription over long distances

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    Promoters and enhancers have long been regarded as distinct elements, a notion that has been challenged more recently. Two new studies now identify promoters that function as long-range enhancers in vivo to regulate the transcription of distal genes.
  19. Reevaluation of SNP heritability in complex human traits

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    By analyzing imputed genetic data for 42 human traits, Doug Speed and colleagues derive a model that describes how heritability varies with minor allele frequency, linkage disequilibrium and genotype certainty. Using this model, they show that common SNPs contribute substantially more heritability than previously thought.

  20. The Cancer Genome Atlas Pan-Cancer analysis project Open

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    Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases.

  21. Neuroblastoma is composed of two super-enhancer-associated differentiation states

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    Rogier Versteeg, Johan van Nes and colleagues report that neuroblastomas comprise two cell types, mesenchymal and adrenergic, that have different responses to chemotherapeutic agents in vitro. Using ChIP–seq and expression profiling of pairs of phenotypically divergent isogenic cell lines, they identify candidate transcription factors for regulation of the two cell states.

  22. Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch Open

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    Victor Albert, Petri Auvinen, Ykä Helariutta, Jaakko Kangasjärvi and colleagues report the reference genome of the silver birch (Betula pendula) and resequencing of 150 birch individuals. They infer past population size crashes consistent with historical periods of climatic change and identify candidate targets of more recent positive selection.

  23. The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability

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    Jeffrey Barrett, Tarjinder Singh and colleagues present a meta-analysis of rare coding variants and copy number variants in a large collection of schizophrenia cases and controls, combined with de novo mutation data from family trios. They find that rare, damaging variants contribute to risk of schizophrenia both with and without intellectual disability and that there is overlap between genetic risk for schizophrenia and other neurodevelopmental disorders.

  24. Between-region genetic divergence reflects the mode and tempo of tumor evolution

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    Christina Curtis and colleagues simulate spatial tumor growth under different evolutionary models and compare their results to multiregion sequencing data. They find that it is possible to distinguish tumors driven by strong positive selection from those evolving neutrally or under weak selection and infer different evolutionary modes within and between tumor types.

  25. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

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    Christopher Amos and colleagues perform genome-wide association analysis for lung cancer using cohorts genotyped on the OncoArray and combing these with existing data. They identify 18 loci, 10 of which are new, finding heterogeneity across the different lung cancer subtypes, and explore candidate genes through eQTL analysis in lung tissue.