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Volume 613 Issue 7944, 19 January 2023

Lines of descent

The historic isolation of Finland’s population has resulted in a genetic make-up that is relatively homogeneous (as illustrated on the cover). In this week’s issue, two papers make use of Finland’s unique heritage to probe the genetics of disease. At the heart of this work is the FinnGen study, which aims to explore the genomes and health data of 500,000 Finns. The first paper analyses data from 224,737 Finns, finding 1,838 genetic variants that influence 681 different diseases. These include 702 potentially novel, low-frequency variant associations. The second paper focuses on recessive conditions — in which the genes inherited from each parent must both be defective to cause disease — finding a number of Finnish-specific associations and uncovering a larger complexity of genetic inheritance than previously appreciated.

Cover image: Federico Simeoni, Małgorzata Nowicka, Nicola Cerioli, Rupesh Vyas

This Week

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News in Focus

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  • News & Views

    • Mouse and human embryos undergo similar developmental steps, but the exact timings differ. An analysis reveals that differences in metabolic activity set the timing of one such step on the road to formation of the vertebrae.

      • Katharina Sonnen
      News & Views
    • T cells of the immune system develop through a lineage-commitment step followed by two checkpoints. The finding that the first checkpoint is needed to complete commitment offers a fresh perspective on T-cell development.

      • Ellen V. Rothenberg
      News & Views
    • How does a fruit fly’s brain determine which way the animal should escape in the face of a looming predator? A mechanism involving numeric gradients of synaptic connections between neurons provides an answer.

      • Daniel Tomsic
      • Jamie Theobald
      News & Views
    • Organic electrochemical transistors could be better than conventional inorganic devices for certain uses, but have been held back by performance issues. The solution could be to build up these organic transistors like a sandwich.

      • Camille Cunin
      • Aristide Gumyusenge
      News & Views
    • An analysis of the publication records of academic editors shows that one-quarter of them publish 10% of their own papers in the journals they edit and reveals that fewer than 10% of editors-in-chief are women.

      • Molly M. King
      News & Views
  • Reviews

  • Articles

    • An emergent randomness arising from partial measurement of an interacting many-body system is uncovered, and a widely applicable fidelity estimation scheme is presented that works at shorter evolution times and with reduced experimental complexity.

      • Joonhee Choi
      • Adam L. Shaw
      • Manuel Endres
    • Chiral metasurfaces have been produced, with experimental observation of intrinsic chiral bound states in the continuum, which may lead to applications in chiral light sources and detectors, chiral sensing, valleytronics and asymmetric photocatalysis.

      • Yang Chen
      • Huachun Deng
      • Cheng-Wei Qiu
    • The authors report observation of tunnelling magnetoresistance in an all-antiferromagnetic tunnel junction consisting of Mn3Sn/MgO/Mn3Sn, laying the foundation for the development of ultrafast and efficient spintronic devices using antiferromagnets.

      • Xianzhe Chen
      • Tomoya Higo
      • Satoru Nakatsuji
      Article Open Access
    • Vertical organic electrochemical transistors demonstrating unprecedented performances in both p- and n-type operation modes have been synthesized from new electro-active and ion-permeable semiconducting polymers by the interface engineering of electro-active blend layers.

      • Wei Huang
      • Jianhua Chen
      • Antonio Facchetti
      Article Open Access
    • A reconstruction of temperatures in central and north Greenland from ad 1000 to 2011 shows that that the final decade of this period was on average 1.5 ± 0.4 °C warmer compared to pre-industrial temperatures, accompanied by increased meltwater run-off.

      • M. Hörhold
      • T. Münch
      • T. Laepple
      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
    • An analysis of biobank data from the FinnGen project examines dosage effects of genetic variants on disease, andidentifies a benefit when considering more complex inheritance in the genetics of common as well as Mendelian diseases.

      • H. O. Heyne
      • J. Karjalainen
      • M. J. Daly


      Article Open Access
    • Analysis of behaviour, physiology, anatomy and connectomics in Drosophila shows how direction-specific visual information is transformed onto downstream premotor networks and converted into appropriate motor responses.

      • Mark Dombrovski
      • Martin Y. Peek
      • Gwyneth M. Card
      Article Open Access
    • Mapping of the mouse cerebellar cortex using 3D reconstruction from electron microscopy, as well as numerical simulation of neuronal activity, shows non-random redundancy of connectivity that may favour resilient learning over encoding capacity.

      • Tri M. Nguyen
      • Logan A. Thomas
      • Wei-Chung Allen Lee
    • An in vitro system that recapitulates temporal characteristics of embryonic development demonstrates that the different rates of mouse and human embryonic development stem from differences in metabolic rates and—further downstream—the global rate of protein synthesis.

      • Margarete Diaz-Cuadros
      • Teemu P. Miettinen
      • Olivier Pourquié
    • Single-molecule calibrated live microscopy and computational modelling have revealed that human nuclear pore complex assembly takes different pathways during the exit from mitosis and during nuclear growth in interphase.

      • Shotaro Otsuka
      • Jeremy O. B. Tempkin
      • Jan Ellenberg
      Article Open Access
    • Structural analysis of Cas12a2, a CRISPR-associated nuclease that nonspecifically cleaves ssRNA, ssDNA and dsDNA, reveals a complete activation pathway involved in the abortive infection system protecting cells against invasion.

      • Jack P. K. Bravo
      • Thomson Hallmark
      • David W. Taylor
      Article Open Access
    • RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

      • Oleg Dmytrenko
      • Gina C. Neumann
      • Chase L. Beisel
      Article Open Access
    • We report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with NEK7 and ASC, and propose that the role of NEK7 is to transform NLRP3 into the active NLRP3 inflammasome disc.

      • Le Xiao
      • Venkat Giri Magupalli
      • Hao Wu
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