Genetics

  • Article
    | Open Access

    Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.

    • Paula Dominguez-Salas
    • , Sophie E. Moore
    •  & Branwen J. Hennig
  • Article |

    Genomic rearrangements have important functional consequences for cancer. Here, Choi and Meyerson use CRISPR/Cas technology to generate translocations and inversions that are known drivers of lung cancer, and demonstrate the utility of this technology for studying the role of genomic rearrangements in disease.

    • Peter S. Choi
    •  & Matthew Meyerson
  • Article |

    Mass mortality events of fish and invertebrates are increasingly frequent in coastal zones, yet it is often difficult to identify their causes. Here, the authors provide evidence that a combined field and genomics approach could help identifying the specific cause of mass mortality events.

    • Pierre De Wit
    • , Laura Rogers-Bennett
    •  & Stephen R. Palumbi
  • Article
    | Open Access

    Large-scale efforts are put into the generation of knockout mutant mice for many individual genes. Here, the authors systematically screen skin from 538 mutant mice and identify 50 mutants with epidermal phenotypes, of which 9 are also associated with human skin defects.

    • Kifayathullah Liakath-Ali
    • , Valerie E. Vancollie
    •  & Fiona M. Watt
  • Article
    | Open Access

    Autism spectrum disorder (ASD) is a complex genetic trait that encompasses a range of neurodevelopmental disorders. Here, the authors clone brain-expressed alternatively-spliced isoforms of ASD risk factors and construct a network of protein interactions that provides further insight into the disease aetiology.

    • Roser Corominas
    • , Xinping Yang
    •  & Lilia M. Iakoucheva
  • Article
    | Open Access

    Mass spectrometry (MS) has furthered our understanding of MHC class I-associated peptides (MIPs), but the technique is inadequate for studying MIP-associated polymorphisms. Here, the authors combine high-throughput MS with exome and transcriptome sequencing to identify polymorphic MIPs from two female siblings.

    • Diana Paola Granados
    • , Dev Sriranganadane
    •  & Claude Perreault
  • Article |

    Proteins involved in epigenetic regulation are frequently mutated in several paediatric cancers. Here, Huether et al.characterize the somatic mutation frequency across 21 paediatric cancer subtypes by sequencing 633 epigenetic genes in over 1,000 tumours; generating a rich data set for investigating epigenetic dysregulation.

    • Robert Huether
    • , Li Dong
    •  & James R. Downing
  • Article |

    Epigenetic codes translate external stimuli into targeted and long-lasting gene regulation. In this study, the authors show that regenerative retrograde signalling activates the epigenetic modifying enzyme PCAF, inducing gene expression and promoting axon regeneration in a mouse spinal cord injury model.

    • Radhika Puttagunta
    • , Andrea Tedeschi
    •  & Simone Di Giovanni
  • Article |

    Pulmonary carcinoids account for about 2% of pulmonary neoplasms. Here, the authors carry out gene copy number analysis, genome/exome, and transcriptome sequencing of pulmonary carcinoids and identify frequent mutations in chromatin-remodelling genes that can drive tumorigenesis in these tumours.

    • Lynnette Fernandez-Cuesta
    • , Martin Peifer
    •  & Roman K. Thomas
  • Article |

    Cell type classification is commonly used to interpret the connectivity and functional output of neuronal networks. Here, Sümbül et al. combine structural and genetic approaches to provide a higher resolution classification of neuronal subtypes.

    • Uygar Sümbül
    • , Sen Song
    •  & H. Sebastian Seung
  • Article |

    Males and females show unique patterns of gene expression, but it is unclear if this dimorphism is genetically constrained. Here, Hollis et al. use experimental evolution in Drosophila melanogasterto reveal unresolved conflict between the sexes over gene expression caused by sexual selection.

    • Brian Hollis
    • , David Houle
    •  & Laurent Keller
  • Article
    | Open Access

    Plants produce a variety of metabolites that have a critical role in growth and development. Here, the authors carry out a genome-wide association analysis of metabolites and metabolite features in maize and identify candidate genes involved in secondary metabolism, and a potential biomarker for the genetic improvement of the crop.

    • Weiwei Wen
    • , Dong Li
    •  & Jianbing Yan
  • Article |

    Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.

    • Thomas W. Mühleisen
    • , Markus Leber
    •  & Sven Cichon
  • Article |

    Cardiomyocyte cell cycle arrest is important for mammalian heart maturation, but the process is poorly understood. Here, the authors use exome sequencing to identify compound heterozygous ALMS1mutations associated with cardiomyocyte replication and provide evidence that Alström protein deficiency impairs postnatal cardiomyocyte cell cycle arrest.

    • Lincoln T. Shenje
    • , Peter Andersen
    •  & Daniel P. Judge
  • Article |

    Lipoproteins such as HDL can bind and transport microRNAs throughout the body. Here the authors provide a new mechanism contributing to the anti-inflammatory effects of HDL by which HDL-associated miR-223 is transferred to endothelial cells, where it inhibits expression of the adhesion molecule ICAM-1.

    • Fatiha Tabet
    • , Kasey C. Vickers
    •  & Kerry-Anne Rye
  • Article |

    Cutaneous melanoma is an aggressive form of skin cancer. Here, the authors show that mutations in the TERT promoter of 287 primary melanomas are associated with age, Breslow thickness and tumour ulceration and frequently occur at sun-exposed sites.

    • Barbara Heidenreich
    • , Eduardo Nagore
    •  & Rajiv Kumar
  • Article
    | Open Access

    The ornamental twin-tail goldfish has a bifurcated caudal skeleton that arose during domestication, but the developmental mechanisms that generate this tail are unknown. Here, Abe et al. show that a mutation in the chordingene affects embryonic dorsal–ventral patterning causing the bifurcated tail skeleton.

    • Gembu Abe
    • , Shu-Hua Lee
    •  & Kinya G. Ota
  • Article |

    It is unclear how interactions between individual genomes affect behaviour and survival in social organisms. Here, Teseo et al. show that genomic interactions between larvae and nursing adults of the clonal ant Cerapachys biroidetermine the proportion of individuals involved in reproduction or cooperation.

    • Serafino Teseo
    • , Nicolas Châline
    •  & Daniel J.C. Kronauer
  • Article
    | Open Access

    Hybrids often show poorer performance than their parents due to conflict between parental genes, but the underlying mechanisms are not well understood. Here, Chen et al. identify three genes that activate immune responses and hinder hybrids growth in rice, a finding that may help rice breeding.

    • Chen Chen
    • , Hao Chen
    •  & Hong-Xuan Lin
  • Article |

    The impact of horizontal gene transfer (HGT) on the evolution of higher eukaryotes is not fully understood. Here the authors suggest that the vertebrate vasodilator, adrenomedullin (ADM), was horizontally acquired by ticks and hypothesize that the HGT of ADM triggers the emergence of a new tick genus.

    • Shiroh Iwanaga
    • , Haruhiko Isawa
    •  & Masao Yuda
  • Article
    | Open Access

    Horizontal transfer of DNA is common among eukaryotes but the vectors involved remain elusive. Here, Gilbert et al. show high frequency of in vivotransposition from the cabbage looper moth into genomes of a baculovirus, suggesting that viruses can act as vectors of horizontal transfer between animals.

    • Clément Gilbert
    • , Aurélien Chateigner
    •  & Richard Cordaux
  • Article |

    Defects in the homologous recombination repair of DNA can result in gene mutation and cancer. In this study, Peng et al.identify a gene signature associated with homologous recombination repair deficiency and show that this can be used both to predict repair defects and clinical outcome in cancer patients.

    • Guang Peng
    • , Curtis Chun-Jen Lin
    •  & Shiaw-Yih Lin
  • Article |

    N-methyl-D-aspartate receptors (NMDARs) are key regulators of neuronal excitability in the brain and NMDAR mutations are implicated in epilepsy. Here, the authors identify a NMDAR subunit mutation in a child with epileptic encephalopathy, and show that this mutation increases the activity of NMDAR channels.

    • Hongjie Yuan
    • , Kasper B. Hansen
    •  & Stephen F. Traynelis
  • Article |

    It is unclear whether the mechanisms giving rise to aggression in animals are conserved across the animal kingdom. Here, the authors show that knockdown of tailless, an orthologue of a mouse gene involved in aggression, leads to increased aggression in Drosophila, suggesting that the molecular mechanisms behind aggression are conserved.

    • Shaun M. Davis
    • , Amanda L. Thomas
    •  & Herman A. Dierick
  • Article
    | Open Access

    Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.

    • J.T. Bell
    • , A.K. Loomis
    •  & T.D. Spector
  • Article |

    Many studies provide evidence of genes that are associated with cancer prognosis but a global view of these genes is lacking. Using data from ‘The Cancer Genome Atlas’, Yang et al.investigate the network properties of prognostic genes and show that these genes tend to be within highly interconnected groups but not the most connected nodes in the gene co-expression network.

    • Yang Yang
    • , Leng Han
    •  & Han Liang
  • Article |

    Ovarian cancer is one of the most common cancers in women and has an average 5-year survival of only 43%. Here, Kanchi et al.describe the germline and somatic mutation spectrum in ovarian cancer patients and identify potential risk variants associated with the disease.

    • Krishna L. Kanchi
    • , Kimberly J. Johnson
    •  & Li Ding
  • Article |

    Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.

    • Thomas Wiesner
    • , Jie He
    •  & Boris C. Bastian
  • Article
    | Open Access

    Multiple myeloma is a malignant plasma cell disorder with a complex molecular pathogenesis. Here, the authors perform whole-exome sequencing, copy-number profiling and cytogenetic analysis in 84 myeloma samples and highlight the diversity and evolution of the mutational profile underlying the disease.

    • Niccolo Bolli
    • , Hervé Avet-Loiseau
    •  & Nikhil C. Munshi
  • Article
    | Open Access

    Locusts are destructive agricultural pests and serve as a model organism for studies of insects. Here, the authors report a draft genome sequence of the migratory locust, Locusta migratoria, and provide insight into genes associated with key survival traits such as phase-change, long-distance migration and feeding.

    • Xianhui Wang
    • , Xiaodong Fang
    •  & Le Kang
  • Article
    | Open Access

    Horizontal gene transfers are known to play an important role in prokaryote evolution but their impact and prevalence in eukaryotes is less clear. Here, the authors sequence the genomes of cheese making fungi P. roqueforti and P. camemberti, and provide evidence for recent horizontal transfers of a large genomic region.

    • Kevin Cheeseman
    • , Jeanne Ropars
    •  & Yves Brygoo