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| Open AccessMalaria protection due to sickle haemoglobin depends on parasite genotype
A strong association has been found between three regions of the Plasmodium falciparum genome and sickle haemoglobin in children with severe malaria, suggesting parasites have adapted to overcome natural host immunity.
- Gavin Band
- , Ellen M. Leffler
- & Dominic P. Kwiatkowski
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Matters Arising |
Phantom epistasis between unlinked loci
- Gibran Hemani
- , Joseph E. Powell
- & Peter M. Visscher
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Article |
Functional genomic landscape of cancer-intrinsic evasion of killing by T cells
Genome-wide CRISPR screens in mouse cancer cell lines are used to identify a core, conserved set of genes and pathways that govern how cancer cells evade killing by cytotoxic T lymphocytes.
- Keith A. Lawson
- , Cristovão M. Sousa
- & Jason Moffat
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Letter |
PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components
mRNA that contains a premature termination codon (PTC) triggers a genetic compensation response that involves both transcription of its homologous genes and degradation of the mutated transcript by the nonsense-mediated decay pathway.
- Zhipeng Ma
- , Peipei Zhu
- & Jun Chen
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Letter |
Species-specific activity of antibacterial drug combinations
Screening pairwise combinations of antibiotics and other drugs against three bacterial pathogens reveals that antagonistic and synergistic drug–drug interactions are specific to microbial species and strains.
- Ana Rita Brochado
- , Anja Telzerow
- & Athanasios Typas
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Letter |
Pairwise and higher-order genetic interactions during the evolution of a tRNA
Mutagenesis of a yeast tRNA shows that the effects of mutations and how they interact varies both in magnitude and sign between genotypes.
- Júlia Domingo
- , Guillaume Diss
- & Ben Lehner
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Article |
ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase
ANKRD16 attenuates neurodegeneration induced by a mutation in the editing domain of alanyl tRNA synthetase by directly accepting mis-activated serine from the synthetase before transfer to the tRNA, establishing a new mechanism by which editing defects are prevented.
- My-Nuong Vo
- , Markus Terrey
- & Susan L. Ackerman
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Letter |
Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling
Random mutagenesis in haploid human cells coupled to quantitative protein measurements with different antibodies is used as a readout for individual cellular phenotypes.
- Markus Brockmann
- , Vincent A. Blomen
- & Thijn R. Brummelkamp
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Letter |
PLA2G16 represents a switch between entry and clearance of Picornaviridae
The phospholipase PLA2G16 is required for the entry of picornaviruses, and in its absence, virus infection is prevented by a galectin-8-mediated process.
- Jacqueline Staring
- , Eleonore von Castelmur
- & Thijn R. Brummelkamp
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Letter |
CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase
Charcot–Marie–Tooth diseases are hereditary peripheral neuropathies for which there are currently no effective therapies; here the type 2D subtype of these diseases is shown to be caused by mutations impeding a signalling pathway necessary for motor neuron survival.
- Weiwei He
- , Ge Bai
- & Xiang-Lei Yang
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Letter |
RETRACTED ARTICLE: Detection and replication of epistasis influencing transcription in humans
Epistasis has rarely been shown among natural polymorphisms in human traits; this research using advanced computation and gene expression data reveals many instances of epistasis between common single nucleotide polymorphisms in humans, with epistasis and the direction of its effect replicating in independent cohorts.
- Gibran Hemani
- , Konstantin Shakhbazov
- & Joseph E. Powell
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Letter |
Genetic incompatibilities are widespread within species
The role that epistasis — non-additive interactions between alleles — plays in shaping population fitness is investigated in Drosophila melanogaster; the raw material to drive reproductive isolation is found to be segregating contemporaneously within species and does not necessarily require the emergence of incompatible mutations independently derived and fixed in allopatry.
- Russell B. Corbett-Detig
- , Jun Zhou
- & Julien F. Ayroles
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Letter |
COUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesis
A cell-autonomous role for the COUP-TFII transcription factor in prostate cancer cells is identified, in which COUP-TFII inhibits TGF-β signalling by binding to SMAD4; COUP-TFII promotes prostate tumorigenesis and metastasis in a mouse model, and is associated with more aggressive disease in human prostate cancers.
- Jun Qin
- , San-Pin Wu
- & Sophia Y. Tsai
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Letter
| Open AccessThe long-range interaction landscape of gene promoters
Chromosome conformation capture carbon copy (5C) is used to look at the relationships between functional elements and distal target genes in 1% of the human genome in three dimensions; the study describes numerous long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites, their genomic distribution and complex interactions.
- Amartya Sanyal
- , Bryan R. Lajoie
- & Job Dekker
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Letter |
Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK
Genetic interaction profiles of human lysine deacetylases are generated by RNA interference knockdown to reveal the involvement of deacetylases in many critical biological processes, including metabolism, the cell cycle and development.
- Yu-yi Lin
- , Samara Kiihl
- & Jef D. Boeke
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News & Views |
Noise rules
The idea that gene variants alone control an organism's traits is overly simple. A study of the effects of gene interactions on the outcomes of random variation in gene expression reveals the complex reality. See Letter p.250
- Hana El-Samad
- & Jonathan S. Weissman
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Letter |
Predicting mutation outcome from early stochastic variation in genetic interaction partners
Mutations sometimes only affect a subset of genetically identical individuals; here, variation in the expression of chaperones and gene duplicates is shown to predict mutation outcome in C. elegans.
- Alejandro Burga
- , M. Olivia Casanueva
- & Ben Lehner
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Article |
Remarkably ancient balanced polymorphisms in a multi-locus gene network
Local adaptations are often governed by several interacting genes scattered throughout the genome. Here a novel type of multi–locus genetic variation is described that has been maintained within a species over a vast period of time. A balanced unlinked gene network polymorphism is dissected that involves galactose utilization in a close relative of baker's yeast.
- Chris Todd Hittinger
- , Paula Gonçalves
- & Antonis Rokas