Genetics

  • Article | | open

    PurR acts as transcriptional repressor of purine biosynthesis genes in some bacterial species. Here, the authors show that purR mutations can arise in Staphylococcus aureus upon exposure to stress, leading to upregulation of fibronectin-binding proteins and increased virulence.

    • Mariya I. Goncheva
    • , Ronald S. Flannagan
    • , Brigid E. Sterling
    • , Holly A. Laakso
    • , Nancy C. Friedrich
    • , Julienne C. Kaiser
    • , David W. Watson
    • , Christy H. Wilson
    • , Jessica R. Sheldon
    • , Martin J. McGavin
    • , Patti K. Kiser
    •  & David E. Heinrichs
  • Article | | open

    Meiotic crossover (CO) landscape differs inter- and intra-species, as well as between sexes. Here, the authors show that male meiosis produces more COs than female in maize and detect CO maturation inefficiency in some genetic backgrounds, which may help to improve breeding efficiency.

    • Cheng Luo
    • , Xiang Li
    • , Qinghua Zhang
    •  & Jianbing Yan
  • Article | | open

    FXR1P is a RNA binding protein involved in muscle development. Here, the authors show that mutations in FXR1 exon 15, which is alternatively spliced in muscle, cause multi-minicore myopathy in humans and in mouse models.

    • María Cristina Estañ
    • , Elisa Fernández-Núñez
    • , Maha S. Zaki
    • , María Isabel Esteban
    • , Sandra Donkervoort
    • , Cynthia Hawkins
    • , José A. Caparros-Martin
    • , Dimah Saade
    • , Ying Hu
    • , Véronique Bolduc
    • , Katherine Ru-Yui Chao
    • , Julián Nevado
    • , Ana Lamuedra
    • , Raquel Largo
    • , Gabriel Herrero-Beaumont
    • , Javier Regadera
    • , Concepción Hernandez-Chico
    • , Eduardo F. Tizzano
    • , Victor Martinez-Glez
    • , Jaime J. Carvajal
    • , Ruiting Zong
    • , David L. Nelson
    • , Ghada A. Otaify
    • , Samia Temtamy
    • , Mona Aglan
    • , Mahmoud Issa
    • , Carsten G. Bönnemann
    • , Pablo Lapunzina
    • , Grace Yoon
    •  & Victor L. Ruiz-Perez
  • Article | | open

    Infection of a cell with influenza B virus (IBV) often results in cell death and the role of surviving cells in pathogenesis is unclear. Here, Dumm et al. generate a recombinant IBV that activates a host-cell reporter to permanently label infected cells, and show that surviving cells are important to preserve epithelial barrier function.

    • Rebekah E. Dumm
    • , Jessica K. Fiege
    • , Barbara M. Waring
    • , Chay T. Kuo
    • , Ryan A. Langlois
    •  & Nicholas S. Heaton
  • Article | | open

    Negative selection removes deleterious genetic variation, and can influence genetic architectures and evolution of complex traits. Here, the authors analyze data from 25 UK Biobank diseases and complex traits, and quantify frequency-dependent genetic architectures which suggests actions of negative selection.

    • Armin P. Schoech
    • , Daniel M. Jordan
    • , Po-Ru Loh
    • , Steven Gazal
    • , Luke J. O’Connor
    • , Daniel J. Balick
    • , Pier F. Palamara
    • , Hilary K. Finucane
    • , Shamil R. Sunyaev
    •  & Alkes L. Price
  • Article | | open

    Viruses can encode genes that regulate the host's translational machinery to their advantage. Here, the authors show that viruses encode ribosomal proteins that can be incorporated into the host’s ribosome and may affect translation.

    • Carolina M. Mizuno
    • , Charlotte Guyomar
    • , Simon Roux
    • , Régis Lavigne
    • , Francisco Rodriguez-Valera
    • , Matthew B. Sullivan
    • , Reynald Gillet
    • , Patrick Forterre
    •  & Mart Krupovic
  • Article | | open

    Here, Depledge et al. use nanopore arrays for direct RNA sequencing to profile the HSV-1 transcriptome in productively infected cells. Sequencing of individual RNAs reveals a highly complex viral transcriptome including mRNAs encoding new viral fusion proteins derived by read-through transcription.

    • Daniel P. Depledge
    • , Kalanghad Puthankalam Srinivas
    • , Tomohiko Sadaoka
    • , Devin Bready
    • , Yasuko Mori
    • , Dimitris G. Placantonakis
    • , Ian Mohr
    •  & Angus C. Wilson
  • Article | | open

    Few approaches for targeted manipulation of the epigenome are available in plants. Here, the authors adapt the dCas9-SunTag system to engineer targeted gene activation and site-specific manipulation of DNA methylation in Arabidopsis.

    • Ashot Papikian
    • , Wanlu Liu
    • , Javier Gallego-Bartolomé
    •  & Steven E. Jacobsen
  • Article | | open

    Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

    • David M. Gay
    • , Rachel A. Ridgway
    • , Miryam Müeller
    • , Michael C. Hodder
    • , Ann Hedley
    • , William Clark
    • , Joshua D. Leach
    • , Rene Jackstadt
    • , Colin Nixon
    • , David J. Huels
    • , Andrew D. Campbell
    • , Thomas G. Bird
    •  & Owen J. Sansom
  • Article | | open

    BCL9 and Pygo are components of Wnt enhanceosome, which facilitates β-catenin-dependent transcription. Here, the authors show that deletion of Bcl9 and Pygo suppresses tumorigenesis and extends disease free survival in two different colorectal cancer models, suggesting a strategy for drugging β-catenin signalling in this cancer.

    • Juliusz Mieszczanek
    • , Laurens M. van Tienen
    • , Ashraf E. K. Ibrahim
    • , Douglas J. Winton
    •  & Mariann Bienz
  • Article | | open

    Targeting histone acetylation modulators (HAMPs) is a promising avenue of drug discovery in cancer research. Here, the authors integrate multi-dimensional genomic profiles to systematically investigate recurrent genomic alterations in HAMPs, identifying potential therapeutic targets for precision epigenetic treatment.

    • Zhongyi Hu
    • , Junzhi Zhou
    • , Junjie Jiang
    • , Jiao Yuan
    • , Youyou Zhang
    • , Xuepeng Wei
    • , Nicki Loo
    • , Yueying Wang
    • , Yutian Pan
    • , Tianli Zhang
    • , Xiaomin Zhong
    • , Meixiao Long
    • , Kathleen T. Montone
    • , Janos L. Tanyi
    • , Yi Fan
    • , Tian-Li Wang
    • , Ie-Ming Shih
    • , Xiaowen Hu
    •  & Lin Zhang
  • Article | | open

    Valyl-tRNA synthetase (VARS) charges valyl-tRNA with the amino acid valine, required for translation. Here, the authors describe a progressive epileptic encephalopathy in individuals from five families carrying biallelic mutations in the VARS gene that leave the enzyme activity partially intact.

    • Jennifer Friedman
    • , Desiree E. Smith
    • , Mahmoud Y. Issa
    • , Valentina Stanley
    • , Rengang Wang
    • , Marisa I. Mendes
    • , Meredith S. Wright
    • , Kristen Wigby
    • , Amber Hildreth
    • , John R. Crawford
    • , Alanna E. Koehler
    • , Shimul Chowdhury
    • , Shareef Nahas
    • , Liting Zhai
    • , Zhiwen Xu
    • , Wing-Sze Lo
    • , Kiely N. James
    • , Damir Musaev
    • , Andrea Accogli
    • , Kether Guerrero
    • , Luan T. Tran
    • , Tarek E. I. Omar
    • , Tawfeg Ben-Omran
    • , David Dimmock
    • , Stephen F. Kingsmore
    • , Gajja S. Salomons
    • , Maha S. Zaki
    • , Geneviève Bernard
    •  & Joseph G. Gleeson
  • Article | | open

    tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

    • Aleksandra Siekierska
    • , Hannah Stamberger
    • , Tine Deconinck
    • , Stephanie N. Oprescu
    • , Michèle Partoens
    • , Yifan Zhang
    • , Jo Sourbron
    • , Elias Adriaenssens
    • , Patrick Mullen
    • , Patrick Wiencek
    • , Katia Hardies
    • , Jeong-Soo Lee
    • , Hoi-Khoanh Giong
    • , Felix Distelmaier
    • , Orly Elpeleg
    • , Katherine L. Helbig
    • , Joseph Hersh
    • , Sedat Isikay
    • , Elizabeth Jordan
    • , Ender Karaca
    • , Angela Kecskes
    • , James R. Lupski
    • , Reka Kovacs-Nagy
    • , Patrick May
    • , Vinodh Narayanan
    • , Manuela Pendziwiat
    • , Keri Ramsey
    • , Sampathkumar Rangasamy
    • , Deepali N. Shinde
    • , Ronen Spiegel
    • , Vincent Timmerman
    • , Sarah von Spiczak
    • , Ingo Helbig
    • , Chris Balak
    • , Newell Belnap
    • , Ana Claasen
    • , Amanda Courtright
    • , Matt de Both
    • , Matthew J. Huentelman
    • , Marcus Naymik
    • , Ryan Richholt
    • , Ashley L. Siniard
    • , Szabolcs Szelinger
    • , David W. Craig
    • , Isabelle Schrauwen
    • , Zaid Afawi
    • , Rudi Balling
    • , Stéphanie Baulac
    • , Nina Barišić
    • , Hande S. Caglayan
    • , Dana Craiu
    • , Rosa Guerrero-López
    • , Renzo Guerrini
    • , Helle Hjalgrim
    • , Johanna Jähn
    • , Karl Martin Klein
    • , Eric Leguern
    • , Johannes R. Lemke
    • , Holger Lerche
    • , Carla Marini
    • , Rikke S. Møller
    • , Hiltrud Muhle
    • , Felix Rosenow
    • , Jose Serratosa
    • , Arvid Suls
    • , Ulrich Stephani
    • , Katalin Štěrbová
    • , Pasquale Striano
    • , Federico Zara
    • , Sarah Weckhuysen
    • , Christopher Francklyn
    • , Anthony Antonellis
    • , Peter de Witte
    •  & Peter De Jonghe
  • Article | | open

    We know a large number of risk SNPs for schizophrenia, but little about how these SNPs contribute to the disorder. Here, the authors use functional genomics to identify risk SNPs that disrupt transcription factor binding and validate the regulatory effects of the transcription factor binding-disrupting SNPs.

    • Yongxia Huo
    • , Shiwu Li
    • , Jiewei Liu
    • , Xiaoyan Li
    •  & Xiong-Jian Luo
  • Article | | open

    Oxytocin is a hormone and neurotransmitter involved in reproductive and social behavior, but the role of oxytocin-related genes in the human brain remains unclear. Here, the authors map oxytocin pathway gene expression and show that it overlaps with brain regions involved in reward and emotional states.

    • Daniel S. Quintana
    • , Jaroslav Rokicki
    • , Dennis van der Meer
    • , Dag Alnæs
    • , Tobias Kaufmann
    • , Aldo Córdova-Palomera
    • , Ingrid Dieset
    • , Ole A. Andreassen
    •  & Lars T. Westlye
  • Article | | open

    When examining the evolution of treatment resistance in breast cancer, perceived genomic changes may be due to clonal evolution or heterogeneous tumors. Here, the authors show that apparent clonal change can in fact be due to pre-treatment heterogeneity, and samples from at least two regions are necessary to detect treatment-induced clonal shifts

    • Jennifer L. Caswell-Jin
    • , Katherine McNamara
    • , Johannes G. Reiter
    • , Ruping Sun
    • , Zheng Hu
    • , Zhicheng Ma
    • , Jie Ding
    • , Carlos J. Suarez
    • , Susanne Tilk
    • , Akshara Raghavendra
    • , Victoria Forte
    • , Suet-Feung Chin
    • , Helen Bardwell
    • , Elena Provenzano
    • , Carlos Caldas
    • , Julie Lang
    • , Robert West
    • , Debu Tripathy
    • , Michael F. Press
    •  & Christina Curtis
  • Article | | open

    High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.

    • Moriah Gidoni
    • , Omri Snir
    • , Ayelet Peres
    • , Pazit Polak
    • , Ida Lindeman
    • , Ivana Mikocziova
    • , Vikas Kumar Sarna
    • , Knut E. A. Lundin
    • , Christopher Clouser
    • , Francois Vigneault
    • , Andrew M. Collins
    • , Ludvig M. Sollid
    •  & Gur Yaari
  • Article | | open

    Few tools exist to study molecular diversity during neurodevelopment. Here the authors apply a genetic immortalization method in Drosophila to generate a fate map of olfactory sensory lineages, examine the relationships of this map and the neuroanatomical, molecular and evolutionary properties of the mature circuits, and identify a novel factor controlling lineage development.

    • Phing Chian Chai
    • , Steeve Cruchet
    • , Leonore Wigger
    •  & Richard Benton
  • Article | | open

    Transposable element (TE) bursts shape genome evolution but their origin remains unclear. Here, the authors show that a burst is restricted to only a few domesticated rice accessions and is associated with the acquisition of two TE variants, Ping16A and Ping16A_Stow, not the loss of TE silencing.

    • Jinfeng Chen
    • , Lu Lu
    • , Jazmine Benjamin
    • , Stephanie Diaz
    • , C. Nathan Hancock
    • , Jason E. Stajich
    •  & Susan R. Wessler
  • Article | | open

    Despite the importance of proximal-distal patterning of leaves in cereal productivity, the underlying molecular mechanisms are poorly understood. Here, the authors find that the ratio of sheath to blade in rice leaf shifts depends on the expression levels of BLADE-ON-PETIOLE genes.

    • Taiyo Toriba
    • , Hiroki Tokunaga
    • , Toshihide Shiga
    • , Fanyu Nie
    • , Satoshi Naramoto
    • , Eriko Honda
    • , Keisuke Tanaka
    • , Teruaki Taji
    • , Jun-Ichi Itoh
    •  & Junko Kyozuka
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    Host genetics modulates gut microbiota composition, which in turn affects host health, but little is known about the specific genes involved. Here, Berg et al. show that TGFβ/BMP immune signalling affects abundance and function of commensal Enterobacter species in C. elegans.

    • Maureen Berg
    • , David Monnin
    • , Juhyun Cho
    • , Lydia Nelson
    • , Alex Crits-Christoph
    •  & Michael Shapira
  • Article | | open

    Gene transfer agents (GTAs) are ‘domesticated’ bacteriophages that can transfer any genes between bacteria. Here, Paul Fogg identifies a protein that directly regulates transcription of GTA genes and whose expression is in turn controlled by a global cell-cycle regulator and a quorum-sensing regulator.

    • Paul C. M. Fogg
  • Article | | open

    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is driven by SMARCA4 loss. Here the authors demonstrate that SCCOHT cells are highly sensitive to CDK4/6 inhibition and provide mechanistic insights, whereby this druggable vulnerability is driven by cyclin D1 deficiency induced by SMARCA4 loss.

    • Yibo Xue
    • , Brian Meehan
    • , Elizabeth Macdonald
    • , Sriram Venneti
    • , Xue Qing D. Wang
    • , Leora Witkowski
    • , Petar Jelinic
    • , Tim Kong
    • , Daniel Martinez
    • , Geneviève Morin
    • , Michelle Firlit
    • , Atefeh Abedini
    • , Radia M. Johnson
    • , Regina Cencic
    • , Jay Patibandla
    • , Hongbo Chen
    • , Andreas I. Papadakis
    • , Aurelie Auguste
    • , Iris de Rink
    • , Ron M. Kerkhoven
    • , Nicholas Bertos
    • , Walter H. Gotlieb
    • , Blaise A. Clarke
    • , Alexandra Leary
    • , Michael Witcher
    • , Marie-Christine Guiot
    • , Jerry Pelletier
    • , Josée Dostie
    • , Morag Park
    • , Alexander R. Judkins
    • , Ralf Hass
    • , Douglas A. Levine
    • , Janusz Rak
    • , Barbara Vanderhyden
    • , William D. Foulkes
    •  & Sidong Huang
  • Article | | open

    N6-methyladenine is involved in many biological pathways for microbial survival and host interaction. Here the authors train a neural network for improved m6A detection in nanopore sequencing data and validate methylomes for a microbial reference community.

    • Alexa B. R. McIntyre
    • , Noah Alexander
    • , Kirill Grigorev
    • , Daniela Bezdan
    • , Heike Sichtig
    • , Charles Y. Chiu
    •  & Christopher E. Mason
  • Article | | open

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    • , Zhaoyu Zhang
    • , Xi Chen
    • , Xiangzhi Zeng
    • , Yiyang Zhang
    • , Tingyue Deng
    • , Mengfei Ren
    • , Zheng Sun
    • , Rui Jiang
    •  & Zhen Xie
  • Article | | open

    The Caucasus mountain range has impacted on the culture and genetics of the wider region. Here, the authors generate genome-wide SNP data for 45 Eneolithic and Bronze Age individuals across the Caucasus, and find distinct genetic clusters between mountain and steppe zones as well as occasional gene-flow.

    • Chuan-Chao Wang
    • , Sabine Reinhold
    • , Alexey Kalmykov
    • , Antje Wissgott
    • , Guido Brandt
    • , Choongwon Jeong
    • , Olivia Cheronet
    • , Matthew Ferry
    • , Eadaoin Harney
    • , Denise Keating
    • , Swapan Mallick
    • , Nadin Rohland
    • , Kristin Stewardson
    • , Anatoly R. Kantorovich
    • , Vladimir E. Maslov
    • , Vladimira G. Petrenko
    • , Vladimir R. Erlikh
    • , Biaslan Ch. Atabiev
    • , Rabadan G. Magomedov
    • , Philipp L. Kohl
    • , Kurt W. Alt
    • , Sandra L. Pichler
    • , Claudia Gerling
    • , Harald Meller
    • , Benik Vardanyan
    • , Larisa Yeganyan
    • , Alexey D. Rezepkin
    • , Dirk Mariaschk
    • , Natalia Berezina
    • , Julia Gresky
    • , Katharina Fuchs
    • , Corina Knipper
    • , Stephan Schiffels
    • , Elena Balanovska
    • , Oleg Balanovsky
    • , Iain Mathieson
    • , Thomas Higham
    • , Yakov B. Berezin
    • , Alexandra Buzhilova
    • , Viktor Trifonov
    • , Ron Pinhasi
    • , Andrej B. Belinskij
    • , David Reich
    • , Svend Hansen
    • , Johannes Krause
    •  & Wolfgang Haak
  • Article | | open

    Information of genetic architectures of complex traits can be leveraged for predicting phenotypes. Here, the authors develop CTPR (Cross-Trait Penalized Regression), a method for multi-trait polygenic risk prediction using individual-level genotypes and/or summary statistics from large cohorts.

    • Wonil Chung
    • , Jun Chen
    • , Constance Turman
    • , Sara Lindstrom
    • , Zhaozhong Zhu
    • , Po-Ru Loh
    • , Peter Kraft
    •  & Liming Liang
  • Article | | open

    Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

    • Armand Valsesia
    • , Qiao-Ping Wang
    • , Nele Gheldof
    • , Jérôme Carayol
    • , Hélène Ruffieux
    • , Teleri Clark
    • , Victoria Shenton
    • , Lisa J. Oyston
    • , Gregory Lefebvre
    • , Sylviane Metairon
    • , Christian Chabert
    • , Ondine Walter
    • , Polina Mironova
    • , Paulina Lau
    • , Patrick Descombes
    • , Nathalie Viguerie
    • , Dominique Langin
    • , Mary-Ellen Harper
    • , Arne Astrup
    • , Wim H. Saris
    • , Robert Dent
    • , Greg G. Neely
    •  & Jörg Hager
  • Article | | open

    Previous surveys of global ocean microbial diversity have focused on planktonic microbes. Here, Zhang et al. use metagenomics to study biofilm-forming marine microbes, increasing the known microbial diversity in the oceans by more than 20% and revealing new biosynthetic gene clusters and CRISPR-Cas systems.

    • Weipeng Zhang
    • , Wei Ding
    • , Yong-Xin Li
    • , Chunkit Tam
    • , Salim Bougouffa
    • , Ruojun Wang
    • , Bite Pei
    • , Hoyin Chiang
    • , Pokman Leung
    • , Yanhong Lu
    • , Jin Sun
    • , He Fu
    • , Vladimir B Bajic
    • , Hongbin Liu
    • , Nicole S. Webster
    •  & Pei-Yuan Qian
  • Article | | open

    Adeno-associated viral vectors (AAV) are being developed for gene therapy of skeletal muscle, but it is a challenge to achieve robust gene expression. Here, the authors identify muscle-specific cisregulatory elements that lead to a substantial increase in micro-dystrophin and follistatin expression, resulting in a safe and sustainable rescue of the dystrophic phenotype in mouse models.

    • S. Sarcar
    • , W. Tulalamba
    • , M. Y. Rincon
    • , J. Tipanee
    • , H. Q. Pham
    • , H. Evens
    • , D. Boon
    • , E. Samara-Kuko
    • , M. Keyaerts
    • , M. Loperfido
    • , E. Berardi
    • , S. Jarmin
    • , P. In’t Veld
    • , G. Dickson
    • , T. Lahoutte
    • , M. Sampaolesi
    • , P. De Bleser
    • , T. VandenDriessche
    •  & M. K. Chuah
  • Article | | open

    Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.

    • Gregory M. LaMonte
    • , Pamela Orjuela-Sanchez
    • , Jaeson Calla
    • , Lawrence T. Wang
    • , Shangzhong Li
    • , Justine Swann
    • , Annie N. Cowell
    • , Bing Yu Zou
    • , Alyaa M. Abdel-Haleem Mohamed
    • , Zaira Hellen Villa Galarce
    • , Marta Moreno
    • , Carlos Tong Rios
    • , Joseph M. Vinetz
    • , Nathan Lewis
    •  & Elizabeth A. Winzeler
  • Article | | open

    Mammalian transcription factors (TFs) differ broadly in their DNA binding properties. Here authors quantify mitotic chromosome binding (MCB) of 501 TFs and suggest that MCB can be used as a proxy for non-specific TF-DNA interactions that regulate TF search for specific genomic sites.

    • Mahé Raccaud
    • , Elias T. Friman
    • , Andrea B. Alber
    • , Harsha Agarwal
    • , Cédric Deluz
    • , Timo Kuhn
    • , J. Christof M. Gebhardt
    •  & David M. Suter
  • Article | | open

    GWAS have previously found 24 genomic loci associated with chronotype, an individual’s preference for early or late sleep timing. Here, the authors identify 327 additional loci in a sample of 697,828 individuals and further explore the relationships of chronotype with metabolic and psychiatric diseases.

    • Samuel E. Jones
    • , Jacqueline M. Lane
    • , Andrew R. Wood
    • , Vincent T. van Hees
    • , Jessica Tyrrell
    • , Robin N. Beaumont
    • , Aaron R. Jeffries
    • , Hassan S. Dashti
    • , Melvyn Hillsdon
    • , Katherine S. Ruth
    • , Marcus A. Tuke
    • , Hanieh Yaghootkar
    • , Seth A. Sharp
    • , Yingjie Jie
    • , William D. Thompson
    • , Jamie W. Harrison
    • , Amy Dawes
    • , Enda M. Byrne
    • , Henning Tiemeier
    • , Karla V. Allebrandt
    • , Jack Bowden
    • , David W. Ray
    • , Rachel M. Freathy
    • , Anna Murray
    • , Diego R. Mazzotti
    • , Philip R. Gehrman
    • , Debbie A. Lawlor
    • , Timothy M. Frayling
    • , Martin K. Rutter
    • , David A. Hinds
    • , Richa Saxena
    •  & Michael N. Weedon
  • Article | | open

    Heterogeneity in gene expression and epigenetic states exists across individual cells. Here, the authors develop scCAT-seq, a technique for simultaneously performing ATAC-seq and RNA-seq within the same single cell.

    • Longqi Liu
    • , Chuanyu Liu
    • , Andrés Quintero
    • , Liang Wu
    • , Yue Yuan
    • , Mingyue Wang
    • , Mengnan Cheng
    • , Lizhi Leng
    • , Liqin Xu
    • , Guoyi Dong
    • , Rui Li
    • , Yang Liu
    • , Xiaoyu Wei
    • , Jiangshan Xu
    • , Xiaowei Chen
    • , Haorong Lu
    • , Dongsheng Chen
    • , Quanlei Wang
    • , Qing Zhou
    • , Xinxin Lin
    • , Guibo Li
    • , Shiping Liu
    • , Qi Wang
    • , Hongru Wang
    • , J. Lynn Fink
    • , Zhengliang Gao
    • , Xin Liu
    • , Yong Hou
    • , Shida Zhu
    • , Huanming Yang
    • , Yunming Ye
    • , Ge Lin
    • , Fang Chen
    • , Carl Herrmann
    • , Roland Eils
    • , Zhouchun Shang
    •  & Xun Xu
  • Article | | open

    Most cyanobacteria are oxygenic photoautotrophs, and fermenters under dark anoxic conditions. Here, the authors analyse genomic sequences of related uncultivated bacteria, inferring their metabolic potential, and supporting that their common ancestor was an anaerobe capable of fermentation and H2 metabolism.

    • Paula B. Matheus Carnevali
    • , Frederik Schulz
    • , Cindy J. Castelle
    • , Rose S. Kantor
    • , Patrick M. Shih
    • , Itai Sharon
    • , Joanne M. Santini
    • , Matthew R. Olm
    • , Yuki Amano
    • , Brian C. Thomas
    • , Karthik Anantharaman
    • , David Burstein
    • , Eric D. Becraft
    • , Ramunas Stepanauskas
    • , Tanja Woyke
    •  & Jillian F. Banfield
  • Article | | open

    The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.

    • Alice Neal
    • , Svanhild Nornes
    • , Sophie Payne
    • , Marsha D. Wallace
    • , Martin Fritzsche
    • , Pakavarin Louphrasitthiphol
    • , Robert N. Wilkinson
    • , Kira M. Chouliaras
    • , Ke Liu
    • , Karen Plant
    • , Radhika Sholapurkar
    • , Indrika Ratnayaka
    • , Wiebke Herzog
    • , Gareth Bond
    • , Tim Chico
    • , George Bou-Gharios
    •  & Sarah De Val
  • Article | | open

    The inactive X chromosome (Xi) is a model for establishment and maintenance of repressed chromatin and the function of polycomb repressive complexes. Here the authors show that Xi transiently relocates from the nuclear periphery during replication in a CIZ1-dependent manner, which plays a role in maintaining PRC-mediated repressed chromatin.

    • Emma R. Stewart
    • , Robert M. L. Turner
    • , Katherine Newling
    • , Rebeca Ridings-Figueroa
    • , Victoria Scott
    • , Peter D. Ashton
    • , Justin F. X. Ainscough
    •  & Dawn Coverley
  • Article | | open

    Broomcorn millet is one of the earliest domesticated plants and has the highest water use efficiency among cereals. Here, the authors report its genome assembly and annotation, which provides a valuable resource for breeders and paves the way for studying plant drought tolerance and C4 photosynthesis.

    • Changsong Zou
    • , Leiting Li
    • , Daisuke Miki
    • , Delin Li
    • , Qiming Tang
    • , Lihong Xiao
    • , Santosh Rajput
    • , Ping Deng
    • , Li Peng
    • , Wei Jia
    • , Ru Huang
    • , Meiling Zhang
    • , Yidan Sun
    • , Jiamin Hu
    • , Xing Fu
    • , Patrick S. Schnable
    • , Yuxiao Chang
    • , Feng Li
    • , Hui Zhang
    • , Baili Feng
    • , Xinguang Zhu
    • , Renyi Liu
    • , James C. Schnable
    • , Jian-Kang Zhu
    •  & Heng Zhang
  • Article | | open

    Multiple morphological abnormalities of the sperm flagella (MMAF) is a cause of male infertility. Here the authors identify homozygous nonsense mutations of the glutamine rich 2 (QRICH2) gene in two MMAF patients from 2 consanguineous families and show using QRICH2 knockout mice that the protein is required for sperm flagellar formation and motility.

    • Ying Shen
    • , Feng Zhang
    • , Fuping Li
    • , Xiaohui Jiang
    • , Yihong Yang
    • , Xiaoliang Li
    • , Weiyu Li
    • , Xiang Wang
    • , Juan Cheng
    • , Mohan Liu
    • , Xueguang Zhang
    • , Guiping Yuan
    • , Xue Pei
    • , Kailai Cai
    • , Fengyun Hu
    • , Jianfeng Sun
    • , Lanzhen Yan
    • , Li Tang
    • , Chuan Jiang
    • , Wenling Tu
    • , Jinyan Xu
    • , Haojuan Wu
    • , Weiqi Kong
    • , Shuying Li
    • , Ke Wang
    • , Kai Sheng
    • , Xudong Zhao
    • , Huanxun Yue
    • , Xiaoyu Yang
    •  & Wenming Xu
  • Article | | open

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi
  • Article | | open

    Broomcorn millet is one of the oldest crops cultivated by human that has strong abiotic stress tolerance. To facilitate genome assisted breeding of this and related species, the authors report its genome assembly and conduct comparative genome structure and evolution analyses with foxtail millet.

    • Junpeng Shi
    • , Xuxu Ma
    • , Jihong Zhang
    • , Yingsi Zhou
    • , Minxuan Liu
    • , Liangliang Huang
    • , Silong Sun
    • , Xiangbo Zhang
    • , Xiang Gao
    • , Wei Zhan
    • , Pinghua Li
    • , Lun Wang
    • , Ping Lu
    • , Haiming Zhao
    • , Weibin Song
    •  & Jinsheng Lai
  • Article | | open

    Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

    • Xia Jiang
    • , Hilary K. Finucane
    • , Fredrick R. Schumacher
    • , Stephanie L. Schmit
    • , Jonathan P. Tyrer
    • , Younghun Han
    • , Kyriaki Michailidou
    • , Corina Lesseur
    • , Karoline B. Kuchenbaecker
    • , Joe Dennis
    • , David V. Conti
    • , Graham Casey
    • , Mia M. Gaudet
    • , Jeroen R. Huyghe
    • , Demetrius Albanes
    • , Melinda C. Aldrich
    • , Angeline S. Andrew
    • , Irene L. Andrulis
    • , Hoda Anton-Culver
    • , Antonis C. Antoniou
    • , Natalia N. Antonenkova
    • , Susanne M. Arnold
    • , Kristan J. Aronson
    • , Banu K. Arun
    • , Elisa V. Bandera
    • , Rosa B. Barkardottir
    • , Daniel R. Barnes
    • , Jyotsna Batra
    • , Matthias W. Beckmann
    • , Javier Benitez
    • , Sara Benlloch
    • , Andrew Berchuck
    • , Sonja I. Berndt
    • , Heike Bickeböller
    • , Stephanie A. Bien
    • , Carl Blomqvist
    • , Stefania Boccia
    • , Natalia V. Bogdanova
    • , Stig E. Bojesen
    • , Manjeet K. Bolla
    • , Hiltrud Brauch
    • , Hermann Brenner
    • , James D. Brenton
    • , Mark N. Brook
    • , Joan Brunet
    • , Hans Brunnström
    • , Daniel D. Buchanan
    • , Barbara Burwinkel
    • , Ralf Butzow
    • , Gabriella Cadoni
    • , Trinidad Caldés
    • , Maria A. Caligo
    • , Ian Campbell
    • , Peter T. Campbell
    • , Géraldine Cancel-Tassin
    • , Lisa Cannon-Albright
    • , Daniele Campa
    • , Neil Caporaso
    • , André L. Carvalho
    • , Andrew T. Chan
    • , Jenny Chang-Claude
    • , Stephen J. Chanock
    • , Chu Chen
    • , David C. Christiani
    • , Kathleen B. M. Claes
    • , Frank Claessens
    • , Judith Clements
    • , J. Margriet Collée
    • , Marcia Cruz Correa
    • , Fergus J. Couch
    • , Angela Cox
    • , Julie M. Cunningham
    • , Cezary Cybulski
    • , Kamila Czene
    • , Mary B. Daly
    • , Anna deFazio
    • , Peter Devilee
    • , Orland Diez
    • , Manuela Gago-Dominguez
    • , Jenny L. Donovan
    • , Thilo Dörk
    • , Eric J. Duell
    • , Alison M. Dunning
    • , Miriam Dwek
    • , Diana M. Eccles
    • , Christopher K. Edlund
    • , Digna R Velez Edwards
    • , Carolina Ellberg
    • , D. Gareth Evans
    • , Peter A. Fasching
    • , Robert L. Ferris
    • , Triantafillos Liloglou
    • , Jane C. Figueiredo
    • , Olivia Fletcher
    • , Renée T. Fortner
    • , Florentia Fostira
    • , Silvia Franceschi
    • , Eitan Friedman
    • , Steven J. Gallinger
    • , Patricia A. Ganz
    • , Judy Garber
    • , José A. García-Sáenz
    • , Simon A. Gayther
    • , Graham G. Giles
    • , Andrew K. Godwin
    • , Mark S. Goldberg
    • , David E. Goldgar
    • , Ellen L. Goode
    • , Marc T. Goodman
    • , Gary Goodman
    • , Kjell Grankvist
    • , Mark H. Greene
    • , Henrik Gronberg
    • , Jacek Gronwald
    • , Pascal Guénel
    • , Niclas Håkansson
    • , Per Hall
    • , Ute Hamann
    • , Freddie C. Hamdy
    • , Robert J. Hamilton
    • , Jochen Hampe
    • , Aage Haugen
    • , Florian Heitz
    • , Rolando Herrero
    • , Peter Hillemanns
    • , Michael Hoffmeister
    • , Estrid Høgdall
    • , Yun-Chul Hong
    • , John L. Hopper
    • , Richard Houlston
    • , Peter J. Hulick
    • , David J. Hunter
    • , David G. Huntsman
    • , Gregory Idos
    • , Evgeny N. Imyanitov
    • , Sue Ann Ingles
    • , Claudine Isaacs
    • , Anna Jakubowska
    • , Paul James
    • , Mark A. Jenkins
    • , Mattias Johansson
    • , Mikael Johansson
    • , Esther M. John
    • , Amit D. Joshi
    • , Radka Kaneva
    • , Beth Y. Karlan
    • , Linda E. Kelemen
    • , Tabea Kühl
    • , Kay-Tee Khaw
    • , Elza Khusnutdinova
    • , Adam S. Kibel
    • , Lambertus A. Kiemeney
    • , Jeri Kim
    • , Susanne K. Kjaer
    • , Julia A. Knight
    • , Manolis Kogevinas
    • , Zsofia Kote-Jarai
    • , Stella Koutros
    • , Vessela N. Kristensen
    • , Jolanta Kupryjanczyk
    • , Martin Lacko
    • , Stephan Lam
    • , Diether Lambrechts
    • , Maria Teresa Landi
    • , Philip Lazarus
    • , Nhu D. Le
    • , Eunjung Lee
    • , Flavio Lejbkowicz
    • , Heinz-Josef Lenz
    • , Goska Leslie
    • , Davor Lessel
    • , Jenny Lester
    • , Douglas A. Levine
    • , Li Li
    • , Christopher I. Li
    • , Annika Lindblom
    • , Noralane M. Lindor
    • , Geoffrey Liu
    • , Fotios Loupakis
    • , Jan Lubiński
    • , Lovise Maehle
    • , Christiane Maier
    • , Arto Mannermaa
    • , Loic Le Marchand
    • , Sara Margolin
    • , Taymaa May
    • , Lesley McGuffog
    • , Alfons Meindl
    • , Pooja Middha
    • , Austin Miller
    • , Roger L. Milne
    • , Robert J. MacInnis
    • , Francesmary Modugno
    • , Marco Montagna
    • , Victor Moreno
    • , Kirsten B. Moysich
    • , Lorelei Mucci
    • , Kenneth Muir
    • , Anna Marie Mulligan
    • , Katherine L. Nathanson
    • , David E. Neal
    • , Andrew R. Ness
    • , Susan L. Neuhausen
    • , Heli Nevanlinna
    • , Polly A. Newcomb
    • , Lisa F. Newcomb
    • , Finn Cilius Nielsen
    • , Liene Nikitina-Zake
    • , Børge G. Nordestgaard
    • , Robert L. Nussbaum
    • , Kenneth Offit
    • , Edith Olah
    • , Ali Amin Al Olama
    • , Olufunmilayo I. Olopade
    • , Andrew F. Olshan
    • , Håkan Olsson
    • , Ana Osorio
    • , Hardev Pandha
    • , Jong Y. Park
    • , Nora Pashayan
    • , Michael T. Parsons
    • , Tanja Pejovic
    • , Kathryn L. Penney
    • , Wilbert H M. Peters
    • , Catherine M. Phelan
    • , Amanda I. Phipps
    • , Dijana Plaseska-Karanfilska
    • , Miranda Pring
    • , Darya Prokofyeva
    • , Paolo Radice
    • , Kari Stefansson
    • , Susan J. Ramus
    • , Leon Raskin
    • , Gad Rennert
    • , Hedy S. Rennert
    • , Elizabeth J. van Rensburg
    • , Marjorie J. Riggan
    • , Harvey A. Risch
    • , Angela Risch
    • , Monique J. Roobol
    • , Barry S. Rosenstein
    • , Mary Anne Rossing
    • , Kim De Ruyck
    • , Emmanouil Saloustros
    • , Dale P. Sandler
    • , Elinor J. Sawyer
    • , Matthew B. Schabath
    • , Johanna Schleutker
    • , Marjanka K. Schmidt
    • , V. Wendy Setiawan
    • , Hongbing Shen
    • , Erin M. Siegel
    • , Weiva Sieh
    • , Christian F. Singer
    • , Martha L. Slattery
    • , Karina Dalsgaard Sorensen
    • , Melissa C. Southey
    • , Amanda B. Spurdle
    • , Janet L. Stanford
    • , Victoria L. Stevens
    • , Sebastian Stintzing
    • , Jennifer Stone
    • , Karin Sundfeldt
    • , Rebecca Sutphen
    • , Anthony J. Swerdlow
    • , Eloiza H. Tajara
    • , Catherine M. Tangen
    • , Adonina Tardon
    • , Jack A. Taylor
    • , M. Dawn Teare
    • , Manuel R. Teixeira
    • , Mary Beth Terry
    • , Kathryn L. Terry
    • , Stephen N. Thibodeau
    • , Mads Thomassen
    • , Line Bjørge
    • , Marc Tischkowitz
    • , Amanda E. Toland
    • , Diana Torres
    • , Paul A. Townsend
    • , Ruth C. Travis
    • , Nadine Tung
    • , Shelley S. Tworoger
    • , Cornelia M. Ulrich
    • , Nawaid Usmani
    • , Celine M. Vachon
    • , Els Van Nieuwenhuysen
    • , Ana Vega
    • , Miguel Elías Aguado-Barrera
    • , Qin Wang
    • , Penelope M. Webb
    • , Clarice R. Weinberg
    • , Stephanie Weinstein
    • , Mark C. Weissler
    • , Jeffrey N. Weitzel
    • , Catharine M. L. West
    • , Emily White
    • , Alice S. Whittemore
    • , H-Erich Wichmann
    • , Fredrik Wiklund
    • , Robert Winqvist
    • , Alicja Wolk
    • , Penella Woll
    • , Michael Woods
    • , Anna H. Wu
    • , Xifeng Wu
    • , Drakoulis Yannoukakos
    • , Wei Zheng
    • , Shanbeh Zienolddiny
    • , Argyrios Ziogas
    • , Kristin K. Zorn
    • , Jacqueline M. Lane
    • , Richa Saxena
    • , Duncan Thomas
    • , Rayjean J. Hung
    • , Brenda Diergaarde
    • , James McKay
    • , Ulrike Peters
    • , Li Hsu
    • , Montserrat García-Closas
    • , Rosalind A. Eeles
    • , Georgia Chenevix-Trench
    • , Paul J. Brennan
    • , Christopher A. Haiman
    • , Jacques Simard
    • , Douglas F. Easton
    • , Stephen B. Gruber
    • , Paul D. P. Pharoah
    • , Alkes L. Price
    • , Bogdan Pasaniuc
    • , Christopher I. Amos
    • , Peter Kraft
    •  & Sara Lindström
  • Article | | open

    Transcription factors of the AP-1 family can play diverse roles despite recognizing the same DNA sequence. Here the authors investigate the DNA binding activities of AP-1 members in mouse macrophages and apply a machine learning approach to identify motifs predicted to drive factor-specific binding profiles.

    • Gregory J. Fonseca
    • , Jenhan Tao
    • , Emma M. Westin
    • , Sascha H. Duttke
    • , Nathanael J. Spann
    • , Tobias Strid
    • , Zeyang Shen
    • , Joshua D. Stender
    • , Mashito Sakai
    • , Verena M. Link
    • , Christopher Benner
    •  & Christopher K. Glass
  • Article | | open

    The consequences of microglial activation in the aging human brain remain unknown. This study quantified microglial morphology and density in the elderly human brain to show that cortical microglial activation strongly associates with AD pathogenesis and may be an upstream contributor to cognitive decline via the accumulation of tau pathology.

    • Daniel Felsky
    • , Tina Roostaei
    • , Kwangsik Nho
    • , Shannon L. Risacher
    • , Elizabeth M. Bradshaw
    • , Vlad Petyuk
    • , Julie A. Schneider
    • , Andrew Saykin
    • , David A. Bennett
    •  & Philip L. De Jager
  • Article | | open

    Various types of genetic variation contribute to the etiology of intellectual disability (ID). Here, the authors study a cohort of ID patients enriched for mild ID from Finland, to investigate contributions of rare and common variants associated with ID of different levels of severity.

    • Mitja I. Kurki
    • , Elmo Saarentaus
    • , Olli Pietiläinen
    • , Padhraig Gormley
    • , Dennis Lal
    • , Sini Kerminen
    • , Minna Torniainen-Holm
    • , Eija Hämäläinen
    • , Elisa Rahikkala
    • , Riikka Keski-Filppula
    • , Merja Rauhala
    • , Satu Korpi-Heikkilä
    • , Jonna Komulainen–Ebrahim
    • , Heli Helander
    • , Päivi Vieira
    • , Minna Männikkö
    • , Markku Peltonen
    • , Aki S. Havulinna
    • , Veikko Salomaa
    • , Matti Pirinen
    • , Jaana Suvisaari
    • , Jukka S. Moilanen
    • , Jarmo Körkkö
    • , Outi Kuismin
    • , Mark J. Daly
    •  & Aarno Palotie
  • Article | | open

    ER stress and UPR are implicated in various cancers. Here, the authors show that one of the canonical UPR pathways, IRE1α-XBP1 regulates c-MYC signaling to promote prostate tumorigenesis, and pharmacological inhibition of IRE1α with MKC8866 inhibits prostate cancer growth and synergizes with clinically used prostate cancer drugs.

    • Xia Sheng
    • , Hatice Zeynep Nenseth
    • , Su Qu
    • , Omer F. Kuzu
    • , Turid Frahnow
    • , Lukas Simon
    • , Stephanie Greene
    • , Qingping Zeng
    • , Ladan Fazli
    • , Paul S. Rennie
    • , Ian G. Mills
    • , Håvard Danielsen
    • , Fabian Theis
    • , John B. Patterson
    • , Yang Jin
    •  & Fahri Saatcioglu