Genotype articles within Nature

Featured

  • Analysis
    | Open Access

    Human genetic evidence increases the success rate of drugs from clinical development to approval but we are still far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.

    • Eric Vallabh Minikel
    • , Jeffery L. Painter
    •  & Matthew R. Nelson

  • Article |

    A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

    • Siwei Chen
    • , Laurent C. Francioli
    •  & Konrad J. Karczewski

  • Article
    | Open Access

    An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

    • Wen-Wei Liao
    • , Mobin Asri
    •  & Benedict Paten

  • Article
    | Open Access

    Genome-wide association studies of individuals from an isolated population (data from the Finnish biobank study FinnGen) and consequent meta-analyses facilitate the identification of previously unknown coding variant associations for both rare and common diseases.

    • Mitja I. Kurki
    • , Juha Karjalainen
    •  & Aarno Palotie

  • Article
    | Open Access

    A meta-analysis combining whole-exome sequencing data from UK Biobank participants and imputed genotypes from FinnGen participants enables identification of genetic associations with human disease in the rare and low-frequency allelic spectrum

    • Benjamin B. Sun
    • , Mitja I. Kurki
    •  & Heiko Runz

  • Article
    | Open Access

    Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.

    • Clare Bycroft
    • , Colin Freeman
    •  & Jonathan Marchini

  • Letter |

    A genome-wide association study of approximately 7,000 patients with neurodevelopmental disorders demonstrates that overall risk and clinical presentation in putative monogenic disorders is also influenced by common genetic variants present in the general population.

    • Mari E. K. Niemi
    • , Hilary C. Martin
    •  & Jeffrey C. Barrett

  • Letter |

    Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins.

    • Ron Do
    • , Nathan O. Stitziel
    •  & Sekar Kathiresan

  • Outlook |

    Recent discoveries are redefining the role of the immune system in psoriasis, and may help to unravel the mystery of the disease's origins.

    • Ken Garber

  • Letter |

    Rare truncating mutations in the p53-inducible protein phosphatase PPM1D are shown to be associated with predisposition to breast cancer and ovarian cancer; notably, all of the mutations are mosaic in white blood cells but are not present in tumours, and probably have a gain-of-function effect.

    • Elise Ruark
    • , Katie Snape
    •  & Nazneen Rahman

  • Outlook |

    Population and genetic studies are confirming the link between multiple sclerosis and vitamin D, says Richard Ransohoff.

    • Richard M. Ransohoff

  • News & Views |

    Genetic mutations can cause a type of heart disease called dilated cardiomyopathy, by predisposing the organ to enlarge and function poorly. It has now been found that 27% of cases are due to mutations that disrupt the muscle protein titin.

    • Elizabeth M. McNally

  • News & Views |

    Separating primary from secondary changes in the autistic brain has long been a research goal. With knowledge of wide-ranging molecular deficits, identification of the best therapeutic targets becomes a priority. See Letter p.380

    • Željka Korade
    •  & Károly Mirnics

  • Letter |

    A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here, 33 distinct enhancers within this region are identified, showing that SNPs in one of the enhancers affect STAT1 binding. Furthermore, it is shown that in human vascular endothelial cells the enhancer interval physically interacts with a number of specific loci and that IFN-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.

    • Olivier Harismendy
    • , Dimple Notani
    •  & Kelly A. Frazer

  • Article |

    Impulsive behaviour characterizes several psychiatric diseases and violent behaviour but its origins are complex. Here, exon sequencing focused on fourteen serotonin- and dopamine-related genes identified a mutation in HTR2B, which was associated with psychiatric diseases marked by impulsivity in a Finnish population. The role of this serotonin receptor in impulsivity is further supported by the knockout mouse phenotype.

    • Laura Bevilacqua
    • , Stéphane Doly
    •  & David Goldman

  • Letter |

    Here, single nucleotide variants within the LMO1 locus are shown to be associated with inherited susceptibility to neuroblastoma, a childhood cancer of the sympathetic nervous system. Acquired structural variation in the same locus was also frequently found in neuroblastoma patients, leading to the suggestion that loci identified through genome-wide association studies might be also prone to somatic alterations and therefore identify potential therapy targets and/or biomarkers of tumour aggressiveness.

    • Kai Wang
    • , Sharon J. Diskin
    •  & John M. Maris

  • Article |

    The causes of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood, although the protein TDP-43 seems to be involved. These authors show that the polyglutamine-containing protein ataxin 2 interacts with TDP-43 and is a potent modifier of TDP-43 toxicity. Moreover, intermediate-length polyglutamine expansions in the ataxin 2 gene significantly associate with ALS. These data establish the ataxin 2 gene as a new and relatively common ALS disease susceptibility gene.

    • Andrew C. Elden
    • , Hyung-Jun Kim
    •  & Aaron D. Gitler

  • News & Views |

    Variations in several genes can increase an individual's susceptibility to complex disorders. But what tips the balance to cause the full-blown disease? For Crohn's disease, viruses could provide part of the answer.

    • Alison Simmons

  • Letter |

    Sialic acid acetylesterase (SIAE) is an enzyme that is involved in B-cell activation and is required to maintain immunological tolerance in mice. It is shown here that rare, inherited and functionally defective SIAE variants are associated with a variety of autoimmune diseases in humans. The study provides one of the first examples of the importance of rare genetic variants in complex diseases, such as those involving autoimmunity.

    • Ira Surolia
    • , Stephan P. Pirnie
    •  & Shiv Pillai

  • Letter |

    An extensive genome-wide survey of over 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf, was conducted to shed light on the process of dog diversification. The results reveal that much of genome diversity came from Middle Eastern progenitors, combined with interbreeding with local wolf populations, and that recent evolution involved limited genetic variation to create the phenotypic diversity of modern dogs.

    • Bridgett M. vonHoldt
    • , John P. Pollinger
    •  & Robert K. Wayne

  • Letter |

    The existence of all-female species of whiptail lizard, formed as a hybrid between sexual species, has been known since 1962; however, how the meiotic program is altered to produce diploid eggs while maintaining heterozygosity has remained unclear. Here it is shown in parthenogenetic species that meiosis initiates with twice the number of chromosomes compared to sexual species, and that pairing and recombination takes place between genetically identical sister chromosomes instead of between homologues.

    • Aracely A. Lutes
    • , William B. Neaves
    •  & Peter Baumann

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