Volume 51 Issue 8, August 2019

Volume 51 Issue 8

Uncoupling TAD structure from gene expression

The mountains represent wild-type topologically associating domains (TADs), and the reflection in the water below depicts the rearranged TADs present on Drosophila balancer chromosomes. Although there are many changes in topology (the landscape), these have little effect on gene expression.

See Ghavi-Helm et al.

Image: Artwork by Beata Edyta Mierzwa. Cover Design: Erin Dewalt.

Editorial

  • Editorial |

    Record high temperatures are being seen worldwide, thus placing strains on human health and disrupting the availability of essential resources such as food and water. Aberrant weather patterns in the form of intense storms or prolonged drought have put pressure on our agricultural systems and underscored the need for adaptation to a changing climate across many sectors. Complex problems require complex solutions, and genetic approaches could be a powerful tool for helping to mitigate the effects of climate change.

Correspondence

News & Views

  • News & Views |

    Chromatin loops and domains are major organizational hallmarks of chromosomes. New work suggests, however, that these topological features of the genome are poor global predictors of gene activity, raising questions about their function.

    • Elizabeth H. Finn
    •  & Tom Misteli

Letters

  • Letter |

    Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

    • Hunna J. Watson
    • , Zeynep Yilmaz
    • , Laura M. Thornton
    • , Christopher Hübel
    • , Jonathan R. I. Coleman
    • , Héléna A. Gaspar
    • , Julien Bryois
    • , Anke Hinney
    • , Virpi M. Leppä
    • , Manuel Mattheisen
    • , Sarah E. Medland
    • , Stephan Ripke
    • , Shuyang Yao
    • , Paola Giusti-Rodríguez
    • , Ken B. Hanscombe
    • , Kirstin L. Purves
    • , Roger A. H. Adan
    • , Lars Alfredsson
    • , Tetsuya Ando
    • , Ole A. Andreassen
    • , Jessica H. Baker
    • , Wade H. Berrettini
    • , Ilka Boehm
    • , Claudette Boni
    • , Vesna Boraska Perica
    • , Katharina Buehren
    • , Roland Burghardt
    • , Matteo Cassina
    • , Sven Cichon
    • , Maurizio Clementi
    • , Roger D. Cone
    • , Philippe Courtet
    • , Scott Crow
    • , James J. Crowley
    • , Unna N. Danner
    • , Oliver S. P. Davis
    • , Martina de Zwaan
    • , George Dedoussis
    • , Daniela Degortes
    • , Janiece E. DeSocio
    • , Danielle M. Dick
    • , Dimitris Dikeos
    • , Christian Dina
    • , Monika Dmitrzak-Weglarz
    • , Elisa Docampo
    • , Laramie E. Duncan
    • , Karin Egberts
    • , Stefan Ehrlich
    • , Geòrgia Escaramís
    • , Tõnu Esko
    • , Xavier Estivill
    • , Anne Farmer
    • , Angela Favaro
    • , Fernando Fernández-Aranda
    • , Manfred M. Fichter
    • , Krista Fischer
    • , Manuel Föcker
    • , Lenka Foretova
    • , Andreas J. Forstner
    • , Monica Forzan
    • , Christopher S. Franklin
    • , Steven Gallinger
    • , Ina Giegling
    • , Johanna Giuranna
    • , Fragiskos Gonidakis
    • , Philip Gorwood
    • , Monica Gratacos Mayora
    • , Sébastien Guillaume
    • , Yiran Guo
    • , Hakon Hakonarson
    • , Konstantinos Hatzikotoulas
    • , Joanna Hauser
    • , Johannes Hebebrand
    • , Sietske G. Helder
    • , Stefan Herms
    • , Beate Herpertz-Dahlmann
    • , Wolfgang Herzog
    • , Laura M. Huckins
    • , James I. Hudson
    • , Hartmut Imgart
    • , Hidetoshi Inoko
    • , Vladimir Janout
    • , Susana Jiménez-Murcia
    • , Antonio Julià
    • , Gursharan Kalsi
    • , Deborah Kaminská
    • , Jaakko Kaprio
    • , Leila Karhunen
    • , Andreas Karwautz
    • , Martien J. H. Kas
    • , James L. Kennedy
    • , Anna Keski-Rahkonen
    • , Kirsty Kiezebrink
    • , Youl-Ri Kim
    • , Lars Klareskog
    • , Kelly L. Klump
    • , Gun Peggy S. Knudsen
    • , Maria C. La Via
    • , Stephanie Le Hellard
    • , Robert D. Levitan
    • , Dong Li
    • , Lisa Lilenfeld
    • , Bochao Danae Lin
    • , Jolanta Lissowska
    • , Jurjen Luykx
    • , Pierre J. Magistretti
    • , Mario Maj
    • , Katrin Mannik
    • , Sara Marsal
    • , Christian R. Marshall
    • , Morten Mattingsdal
    • , Sara McDevitt
    • , Peter McGuffin
    • , Andres Metspalu
    • , Ingrid Meulenbelt
    • , Nadia Micali
    • , Karen Mitchell
    • , Alessio Maria Monteleone
    • , Palmiero Monteleone
    • , Melissa A. Munn-Chernoff
    • , Benedetta Nacmias
    • , Marie Navratilova
    • , Ioanna Ntalla
    • , Julie K. O’Toole
    • , Roel A. Ophoff
    • , Leonid Padyukov
    • , Aarno Palotie
    • , Jacques Pantel
    • , Hana Papezova
    • , Dalila Pinto
    • , Raquel Rabionet
    • , Anu Raevuori
    • , Nicolas Ramoz
    • , Ted Reichborn-Kjennerud
    • , Valdo Ricca
    • , Samuli Ripatti
    • , Franziska Ritschel
    • , Marion Roberts
    • , Alessandro Rotondo
    • , Dan Rujescu
    • , Filip Rybakowski
    • , Paolo Santonastaso
    • , André Scherag
    • , Stephen W. Scherer
    • , Ulrike Schmidt
    • , Nicholas J. Schork
    • , Alexandra Schosser
    • , Jochen Seitz
    • , Lenka Slachtova
    • , P. Eline Slagboom
    • , Margarita C. T. Slof-Op ‘t Landt
    • , Agnieszka Slopien
    • , Sandro Sorbi
    • , Beata Świątkowska
    • , Jin P. Szatkiewicz
    • , Ioanna Tachmazidou
    • , Elena Tenconi
    • , Alfonso Tortorella
    • , Federica Tozzi
    • , Janet Treasure
    • , Artemis Tsitsika
    • , Marta Tyszkiewicz-Nwafor
    • , Konstantinos Tziouvas
    • , Annemarie A. van Elburg
    • , Eric F. van Furth
    • , Gudrun Wagner
    • , Esther Walton
    • , Elisabeth Widen
    • , Eleftheria Zeggini
    • , Stephanie Zerwas
    • , Stephan Zipfel
    • , Andrew W. Bergen
    • , Joseph M. Boden
    • , Harry Brandt
    • , Steven Crawford
    • , Katherine A. Halmi
    • , L. John Horwood
    • , Craig Johnson
    • , Allan S. Kaplan
    • , Walter H. Kaye
    • , James E. Mitchell
    • , Catherine M. Olsen
    • , John F. Pearson
    • , Nancy L. Pedersen
    • , Michael Strober
    • , Thomas Werge
    • , David C. Whiteman
    • , D. Blake Woodside
    • , Garret D. Stuber
    • , Scott Gordon
    • , Jakob Grove
    • , Anjali K. Henders
    • , Anders Juréus
    • , Katherine M. Kirk
    • , Janne T. Larsen
    • , Richard Parker
    • , Liselotte Petersen
    • , Jennifer Jordan
    • , Martin Kennedy
    • , Grant W. Montgomery
    • , Tracey D. Wade
    • , Andreas Birgegård
    • , Paul Lichtenstein
    • , Claes Norring
    • , Mikael Landén
    • , Nicholas G. Martin
    • , Preben Bo Mortensen
    • , Patrick F. Sullivan
    • , Gerome Breen
    •  & Cynthia M. Bulik
  • Letter |

    Long-read sequencing identifies a GGC repeat expansion in NOTCH2NLC that is associated with neuronal intranuclear inclusion disease, a progressive neurodegenerative disorder. The expansion results in abnormal anti-sense transcripts that could contribute to disease pathogenesis.

    • Jun Sone
    • , Satomi Mitsuhashi
    • , Atsushi Fujita
    • , Takeshi Mizuguchi
    • , Kohei Hamanaka
    • , Keiko Mori
    • , Haruki Koike
    • , Akihiro Hashiguchi
    • , Hiroshi Takashima
    • , Hiroshi Sugiyama
    • , Yutaka Kohno
    • , Yoshihisa Takiyama
    • , Kengo Maeda
    • , Hiroshi Doi
    • , Shigeru Koyano
    • , Hideyuki Takeuchi
    • , Michi Kawamoto
    • , Nobuo Kohara
    • , Tetsuo Ando
    • , Toshiaki Ieda
    • , Yasushi Kita
    • , Norito Kokubun
    • , Yoshio Tsuboi
    • , Kazutaka Katoh
    • , Yoshihiro Kino
    • , Masahisa Katsuno
    • , Yasushi Iwasaki
    • , Mari Yoshida
    • , Fumiaki Tanaka
    • , Ikuo K. Suzuki
    • , Martin C. Frith
    • , Naomichi Matsumoto
    •  & Gen Sobue

Articles

  • Article |

    Whole-genome sequencing identifies noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and oculopharyngeal myopathy with leukoencephalopathy, three disorders with overlapping clinical features and neuroimaging findings.

    • Hiroyuki Ishiura
    • , Shota Shibata
    • , Jun Yoshimura
    • , Yuta Suzuki
    • , Wei Qu
    • , Koichiro Doi
    • , M. Asem Almansour
    • , Junko Kanda Kikuchi
    • , Makiko Taira
    • , Jun Mitsui
    • , Yuji Takahashi
    • , Yaeko Ichikawa
    • , Tatsuo Mano
    • , Atsushi Iwata
    • , Yasuo Harigaya
    • , Miho Kawabe Matsukawa
    • , Takashi Matsukawa
    • , Masaki Tanaka
    • , Yuichiro Shirota
    • , Ryo Ohtomo
    • , Hisatomo Kowa
    • , Hidetoshi Date
    • , Aki Mitsue
    • , Hiroyuki Hatsuta
    • , Satoru Morimoto
    • , Shigeo Murayama
    • , Yasushi Shiio
    • , Yuko Saito
    • , Akihiko Mitsutake
    • , Mizuho Kawai
    • , Takuya Sasaki
    • , Yusuke Sugiyama
    • , Masashi Hamada
    • , Gaku Ohtomo
    • , Yasuo Terao
    • , Yoshihiko Nakazato
    • , Akitoshi Takeda
    • , Yoshio Sakiyama
    • , Yumi Umeda-Kameyama
    • , Jun Shinmi
    • , Katsuhisa Ogata
    • , Yutaka Kohno
    • , Shen-Yang Lim
    • , Ai Huey Tan
    • , Jun Shimizu
    • , Jun Goto
    • , Ichizo Nishino
    • , Tatsushi Toda
    • , Shinichi Morishita
    •  & Shoji Tsuji
  • Article |

    Exome sequencing identifies loss-of-function CELA2A mutations in families with early-onset atherosclerosis and metabolic syndrome. Functional studies show that CELA2A is a circulating enzyme that reduces platelet activation, triggers insulin secretion and degradation, and increases insulin sensitivity.

    • Fatemehsadat Esteghamat
    • , James S. Broughton
    • , Emily Smith
    • , Rebecca Cardone
    • , Tarun Tyagi
    • , Mateus Guerra
    • , András Szabó
    • , Nelson Ugwu
    • , Mitra V. Mani
    • , Bani Azari
    • , Gerald Kayingo
    • , Sunny Chung
    • , Mohsen Fathzadeh
    • , Ephraim Weiss
    • , Jeffrey Bender
    • , Shrikant Mane
    • , Richard P. Lifton
    • , Adebowale Adeniran
    • , Michael H. Nathanson
    • , Fred S. Gorelick
    • , John Hwa
    • , Miklós Sahin-Tóth
    • , Renata Belfort-DeAguiar
    • , Richard G. Kibbey
    •  & Arya Mani
  • Article |

    The authors use theoretical justifications coupled with extensive simulations to accurately estimate SNP-heritability for 22 complex traits and diseases from the UK Biobank data, irrespective of the underlying genetic architecture of the trait.

    • Kangcheng Hou
    • , Kathryn S. Burch
    • , Arunabha Majumdar
    • , Huwenbo Shi
    • , Nicholas Mancuso
    • , Yue Wu
    • , Sriram Sankararaman
    •  & Bogdan Pasaniuc
  • Article |

    An integrative three-dimensional genomic and transcriptional profiling of four human neural cell types links regulatory elements to their target genes and elucidates the function of noncoding variants in neuropsychiatric disorders.

    • Michael Song
    • , Xiaoyu Yang
    • , Xingjie Ren
    • , Lenka Maliskova
    • , Bingkun Li
    • , Ian R. Jones
    • , Chao Wang
    • , Fadi Jacob
    • , Kenneth Wu
    • , Michela Traglia
    • , Tsz Wai Tam
    • , Kirsty Jamieson
    • , Si-Yao Lu
    • , Guo-Li Ming
    • , Yun Li
    • , Jun Yao
    • , Lauren A. Weiss
    • , Jesse R. Dixon
    • , Luke M. Judge
    • , Bruce R. Conklin
    • , Hongjun Song
    • , Li Gan
    •  & Yin Shen
  • Article |

    Removal of boundary and intra-TAD CTCF-binding sites at the Sox9–Kcnj2 locus in mice leads to TAD fusion but no major changes in gene expression. Gene misexpression and disease phenotypes were obtained through inversions and/or repositioning of TAD boundaries.

    • Alexandra Despang
    • , Robert Schöpflin
    • , Martin Franke
    • , Salaheddine Ali
    • , Ivana Jerković
    • , Christina Paliou
    • , Wing-Lee Chan
    • , Bernd Timmermann
    • , Lars Wittler
    • , Martin Vingron
    • , Stefan Mundlos
    •  & Daniel M. Ibrahim

Amendments & Corrections

  • Author Correction |

    • Patrick Turley
    • , Raymond K. Walters
    • , Omeed Maghzian
    • , Aysu Okbay
    • , James J. Lee
    • , Mark Alan Fontana
    • , Tuan Anh Nguyen-Viet
    • , Robbee Wedow
    • , Meghan Zacher
    • , Nicholas A. Furlotte
    • , Michelle Agee
    • , Babak Alipanahi
    • , Adam Auton
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Pierre Fontanillas
    • , Nicholas A. Furlotte
    • , David A. Hinds
    • , Bethann S. Hromatka
    • , Karen E. Huber
    • , Aaron Kleinman
    • , Nadia K. Litterman
    • , Matthew H. McIntyre
    • , Joanna L. Mountain
    • , Carrie A. M. Northover
    • , J. Fah Sathirapongsasuti
    • , Olga V. Sazonova
    • , Janie F. Shelton
    • , Suyash Shringarpure
    • , Chao Tian
    • , Joyce Y. Tung
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , Steven J. Pitts
    • , Patrik Magnusson
    • , Sven Oskarsson
    • , Magnus Johannesson
    • , Peter M. Visscher
    • , David Laibson
    • , David Cesarini
    • , Benjamin M. Neale
    •  & Daniel J. Benjamin
  • Author Correction |

    • Mark R. Davies
    • , Liam McIntyre
    • , Ankur Mutreja
    • , Jake A. Lacey
    • , John A. Lees
    • , Rebecca J. Towers
    • , Sebastián Duchêne
    • , Pierre R. Smeesters
    • , Hannah R. Frost
    • , David J. Price
    • , Matthew T. G. Holden
    • , Sophia David
    • , Philip M. Giffard
    • , Kate A. Worthing
    • , Anna C. Seale
    • , James A. Berkley
    • , Simon R. Harris
    • , Tania Rivera-Hernandez
    • , Olga Berking
    • , Amanda J. Cork
    • , Rosângela S. L. A. Torres
    • , Trevor Lithgow
    • , Richard A. Strugnell
    • , Rene Bergmann
    • , Patric Nitsche-Schmitz
    • , Gusharan S. Chhatwal
    • , Stephen D. Bentley
    • , John D. Fraser
    • , Nicole J. Moreland
    • , Jonathan R. Carapetis
    • , Andrew C. Steer
    • , Julian Parkhill
    • , Allan Saul
    • , Deborah A. Williamson
    • , Bart J. Currie
    • , Steven Y. C. Tong
    • , Gordon Dougan
    •  & Mark J. Walker