当前期刊: Nature Genetics Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-20
    Jamie E. Craig; Xikun Han; Ayub Qassim; Mark Hassall; Jessica N. Cooke Bailey; Tyler G. Kinzy; Anthony P. Khawaja; Jiyuan An; Henry Marshall; Puya Gharahkhani; Robert P. Igo; Stuart L. Graham; Paul R. Healey; Jue-Sheng Ong; Tiger Zhou; Owen Siggs; Matthew H. Law; Emmanuelle Souzeau; Bronwyn Ridge; Pirro G. Hysi; Kathryn P. Burdon; Richard A. Mills; John Landers; Jonathan B. Ruddle; Ashish Agar; Anna Galanopoulos; Andrew J. R. White; Colin E. Willoughby; Nicholas H. Andrew; Stephen Best; Andrea L. Vincent; Ivan Goldberg; Graham Radford-Smith; Nicholas G. Martin; Grant W. Montgomery; Veronique Vitart; Rene Hoehn; Robert Wojciechowski; Jost B. Jonas; Tin Aung; Louis R. Pasquale; Angela Jane Cree; Sobha Sivaprasad; Neeru A. Vallabh; Ananth C. Viswanathan; Francesca Pasutto; Jonathan L. Haines; Caroline C. W. Klaver; Cornelia M. van Duijn; Robert J. Casson; Paul J. Foster; Peng Tee Khaw; Christopher J. Hammond; David A. Mackey; Paul Mitchell; Andrew J. Lotery; Janey L. Wiggs; Alex W. Hewitt; Stuart MacGregor
    更新日期:2020-01-21
  • Genetic studies of urinary metabolites illuminate mechanisms of detoxification and excretion in humans
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-20
    Pascal Schlosser; Yong Li; Peggy Sekula; Johannes Raffler; Franziska Grundner-Culemann; Maik Pietzner; Yurong Cheng; Matthias Wuttke; Inga Steinbrenner; Ulla T. Schultheiss; Fruzsina Kotsis; Tim Kacprowski; Lukas Forer; Birgit Hausknecht; Arif B. Ekici; Matthias Nauck; Uwe Völker; Gerd Walz; Peter J. Oefner; Florian Kronenberg; Robert P. Mohney; Michael Köttgen; Karsten Suhre; Kai-Uwe Eckardt; Gabi Kastenmüller; Anna Köttgen
    更新日期:2020-01-21
  • Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-20
    Anindita Basak; Mathias Munschauer; Caleb A. Lareau; Kara E. Montbleau; Jacob C. Ulirsch; Christina R. Hartigan; Monica Schenone; John Lian; Yaomei Wang; Yumin Huang; Xianfang Wu; Lee Gehrke; Charles M. Rice; Xiuli An; Helen A. Christou; Narla Mohandas; Steven A. Carr; Jane-Jane Chen; Stuart H. Orkin; Eric S. Lander; Vijay G. Sankaran
    更新日期:2020-01-21
  • Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-13
    Michelle Chan-Seng-Yue; Jaeseung C. Kim; Gavin W. Wilson; Karen Ng; Eugenia Flores Figueroa; Grainne M. O’Kane; Ashton A. Connor; Robert E. Denroche; Robert C. Grant; Jessica McLeod; Julie M. Wilson; Gun Ho Jang; Amy Zhang; Sheng-Ben Liang; Ayelet Borgida; Dianne Chadwick; Sangeetha Kalimuthu; Ilinca Lungu; John M. S. Bartlett; Paul M. Krzyzanowski; Vandana Sandhu; Hervé Tiriac; Fieke E. M. Froeling; Joanna M. Karasinska; James T. Topham; Daniel J. Renouf; David F. Schaeffer; Steven J. M. Jones; Marco A. Marra; Janessa Laskin; Runjan Chetty; Lincoln D. Stein; George Zogopoulos; Benjamin Haibe-Kains; Peter J. Campbell; David A. Tuveson; Jennifer J. Knox; Sandra E. Fischer; Steven Gallinger; Faiyaz Notta
    更新日期:2020-01-14
  • ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-13
    Guotai Xu; Sagar Chhangawala; Emiliano Cocco; Pedram Razavi; Yanyan Cai; Jordan E Otto; Lorenzo Ferrando; Pier Selenica; Erik Ladewig; Carmen Chan; Arnaud Da Cruz Paula; Matthew Witkin; Yuanming Cheng; Jane Park; Cristian Serna-Tamayo; HuiYong Zhao; Fan Wu; Mirna Sallaku; Xuan Qu; Alison Zhao; Clayton K Collings; Andrew R. D’Avino; Komal Jhaveri; Richard Koche; Ross L. Levine; Jorge S. Reis-Filho; Cigall Kadoch; Maurizio Scaltriti; Christina S. Leslie; José Baselga; Eneda Toska
    更新日期:2020-01-14
  • On the existence and functionality of topologically associating domains
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-10
    Jonathan A. Beagan; Jennifer E. Phillips-Cremins
    更新日期:2020-01-10
  • ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-06
    Sankari Nagarajan; Shalini V. Rao; Joseph Sutton; Danya Cheeseman; Shanade Dunn; Evangelia K. Papachristou; Jose-Enrique Gonzalez Prada; Dominique-Laurent Couturier; Sanjeev Kumar; Kamal Kishore; Chandra Sekhar Reddy Chilamakuri; Silvia-Elena Glont; Emily Archer Goode; Cara Brodie; Naomi Guppy; Rachael Natrajan; Alejandra Bruna; Carlos Caldas; Alasdair Russell; Rasmus Siersbæk; Kosuke Yusa; Igor Chernukhin; Jason S. Carroll
    更新日期:2020-01-08
  • Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-07
    Laura Fachal; Hugues Aschard; Jonathan Beesley; Daniel R. Barnes; Jamie Allen; Siddhartha Kar; Karen A. Pooley; Joe Dennis; Kyriaki Michailidou; Constance Turman; Penny Soucy; Audrey Lemaçon; Michael Lush; Jonathan P. Tyrer; Maya Ghoussaini; Mahdi Moradi Marjaneh; Xia Jiang; Simona Agata; Kristiina Aittomäki; M. Rosario Alonso; Irene L. Andrulis; Hoda Anton-Culver; Natalia N. Antonenkova; Adalgeir Arason; Volker Arndt; Kristan J. Aronson; Banu K. Arun; Bernd Auber; Paul L. Auer; Jacopo Azzollini; Judith Balmaña; Rosa B. Barkardottir; Daniel Barrowdale; Alicia Beeghly-Fadiel; Javier Benitez; Marina Bermisheva; Katarzyna Białkowska; Amie M. Blanco; Carl Blomqvist; William Blot; Natalia V. Bogdanova; Stig E. Bojesen; Manjeet K. Bolla; Bernardo Bonanni; Ake Borg; Kristin Bosse; Hiltrud Brauch; Hermann Brenner; Ignacio Briceno; Ian W. Brock; Angela Brooks-Wilson; Thomas Brüning; Barbara Burwinkel; Saundra S. Buys; Qiuyin Cai; Trinidad Caldés; Maria A. Caligo; Nicola J. Camp; Ian Campbell; Federico Canzian; Jason S. Carroll; Brian D. Carter; Jose E. Castelao; Jocelyne Chiquette; Hans Christiansen; Wendy K. Chung; Kathleen B. M. Claes; Christine L. Clarke; J. Margriet Collée; Sten Cornelissen; Fergus J. Couch; Angela Cox; Simon S. Cross; Cezary Cybulski; Kamila Czene; Mary B. Daly; Miguel de la Hoya; Peter Devilee; Orland Diez; Yuan Chun Ding; Gillian S. Dite; Susan M. Domchek; Thilo Dörk; Isabel dos-Santos-Silva; Arnaud Droit; Stéphane Dubois; Martine Dumont; Mercedes Duran; Lorraine Durcan; Miriam Dwek; Diana M. Eccles; Christoph Engel; Mikael Eriksson; D. Gareth Evans; Peter A. Fasching; Olivia Fletcher; Giuseppe Floris; Henrik Flyger; Lenka Foretova; William D. Foulkes; Eitan Friedman; Lin Fritschi; Debra Frost; Marike Gabrielson; Manuela Gago-Dominguez; Gaetana Gambino; Patricia A. Ganz; Susan M. Gapstur; Judy Garber; José A. García-Sáenz; Mia M. Gaudet; Vassilios Georgoulias; Graham G. Giles; Gord Glendon; Andrew K. Godwin; Mark S. Goldberg; David E. Goldgar; Anna González-Neira; Maria Grazia Tibiletti; Mark H. Greene; Mervi Grip; Jacek Gronwald; Anne Grundy; Pascal Guénel; Eric Hahnen; Christopher A. Haiman; Niclas Håkansson; Per Hall; Ute Hamann; Patricia A. Harrington; Jaana M. Hartikainen; Mikael Hartman; Wei He; Catherine S. Healey; Bernadette A. M. Heemskerk-Gerritsen; Jane Heyworth; Peter Hillemanns; Frans B. L. Hogervorst; Antoinette Hollestelle; Maartje J. Hooning; John L. Hopper; Anthony Howell; Guanmengqian Huang; Peter J. Hulick; Evgeny N. Imyanitov; Claudine Isaacs; Motoki Iwasaki; Agnes Jager; Milena Jakimovska; Anna Jakubowska; Paul A. James; Ramunas Janavicius; Rachel C. Jankowitz; Esther M. John; Nichola Johnson; Michael E. Jones; Arja Jukkola-Vuorinen; Audrey Jung; Rudolf Kaaks; Daehee Kang; Pooja Middha Kapoor; Beth Y. Karlan; Renske Keeman; Michael J. Kerin; Elza Khusnutdinova; Johanna I. Kiiski; Judy Kirk; Cari M. Kitahara; Yon-Dschun Ko; Irene Konstantopoulou; Veli-Matti Kosma; Stella Koutros; Katerina Kubelka-Sabit; Ava Kwong; Kyriacos Kyriacou; Yael Laitman; Diether Lambrechts; Eunjung Lee; Goska Leslie; Jenny Lester; Fabienne Lesueur; Annika Lindblom; Wing-Yee Lo; Jirong Long; Artitaya Lophatananon; Jennifer T. Loud; Jan Lubiński; Robert J. MacInnis; Tom Maishman; Enes Makalic; Arto Mannermaa; Mehdi Manoochehri; Siranoush Manoukian; Sara Margolin; Maria Elena Martinez; Keitaro Matsuo; Tabea Maurer; Dimitrios Mavroudis; Rebecca Mayes; Lesley McGuffog; Catriona McLean; Noura Mebirouk; Alfons Meindl; Austin Miller; Nicola Miller; Marco Montagna; Fernando Moreno; Kenneth Muir; Anna Marie Mulligan; Victor M. Muñoz-Garzon; Taru A. Muranen; Steven A. Narod; Rami Nassir; Katherine L. Nathanson; Susan L. Neuhausen; Heli Nevanlinna; Patrick Neven; Finn C. Nielsen; Liene Nikitina-Zake; Aaron Norman; Kenneth Offit; Edith Olah; Olufunmilayo I. Olopade; Håkan Olsson; Nick Orr; Ana Osorio; V. Shane Pankratz; Janos Papp; Sue K. Park; Tjoung-Won Park-Simon; Michael T. Parsons; James Paul; Inge Sokilde Pedersen; Bernard Peissel; Beth Peshkin; Paolo Peterlongo; Julian Peto; Dijana Plaseska-Karanfilska; Karolina Prajzendanc; Ross Prentice; Nadege Presneau; Darya Prokofyeva; Miquel Angel Pujana; Katri Pylkäs; Paolo Radice; Susan J. Ramus; Johanna Rantala; Rohini Rau-Murthy; Gad Rennert; Harvey A. Risch; Mark Robson; Atocha Romero; Maria Rossing; Emmanouil Saloustros; Estela Sánchez-Herrero; Dale P. Sandler; Marta Santamariña; Christobel Saunders; Elinor J. Sawyer; Maren T. Scheuner; Daniel F. Schmidt; Rita K. Schmutzler; Andreas Schneeweiss; Minouk J. Schoemaker; Ben Schöttker; Peter Schürmann; Christopher Scott; Rodney J. Scott; Leigha Senter; Caroline M. Seynaeve; Mitul Shah; Priyanka Sharma; Chen-Yang Shen; Xiao-Ou Shu; Christian F. Singer; Thomas P. Slavin; Snezhana Smichkoska; Melissa C. Southey; John J. Spinelli; Amanda B. Spurdle; Jennifer Stone; Dominique Stoppa-Lyonnet; Christian Sutter; Anthony J. Swerdlow; Rulla M. Tamimi; Yen Yen Tan; William J. Tapper; Jack A. Taylor; Manuel R. Teixeira; Maria Tengström; Soo Hwang Teo; Mary Beth Terry; Alex Teulé; Mads Thomassen; Darcy L. Thull; Marc Tischkowitz; Amanda E. Toland; Rob A. E. M. Tollenaar; Ian Tomlinson; Diana Torres; Gabriela Torres-Mejía; Melissa A. Troester; Thérèse Truong; Nadine Tung; Maria Tzardi; Hans-Ulrich Ulmer; Celine M. Vachon; Christi J. van Asperen; Lizet E. van der Kolk; Elizabeth J. van Rensburg; Ana Vega; Alessandra Viel; Joseph Vijai; Maartje J. Vogel; Qin Wang; Barbara Wappenschmidt; Clarice R. Weinberg; Jeffrey N. Weitzel; Camilla Wendt; Hans Wildiers; Robert Winqvist; Alicja Wolk; Anna H. Wu; Drakoulis Yannoukakos; Yan Zhang; Wei Zheng; David Hunter; Paul D. P. Pharoah; Jenny Chang-Claude; Montserrat García-Closas; Marjanka K. Schmidt; Roger L. Milne; Vessela N. Kristensen; Juliet D. French; Stacey L. Edwards; Antonis C. Antoniou; Georgia Chenevix-Trench; Jacques Simard; Douglas F. Easton; Peter Kraft; Alison M. Dunning
    更新日期:2020-01-07
  • Navigating 2020 and beyond
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-07

    As we usher in a new year of a new decade and ponder what the future will bring for the genetics field, we wish to reflect on some specific areas related to diversity, privacy and genome editing that require attention and vigilance from the community.

    更新日期:2020-01-07
  • RNA isoform screens uncover the essentiality and tumor-suppressor activity of ultraconserved poison exons
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-07
    James D. Thomas; Jacob T. Polaski; Qing Feng; Emma J. De Neef; Emma R. Hoppe; Maria V. McSharry; Joseph Pangallo; Austin M. Gabel; Andrea E. Belleville; Jacqueline Watson; Naomi T. Nkinsi; Alice H. Berger; Robert K. Bradley
    更新日期:2020-01-07
  • Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-06
    Ayesha Noorani; Xiaodun Li; Martin Goddard; Jason Crawte; Ludmil B. Alexandrov; Maria Secrier; Matthew D. Eldridge; Lawrence Bower; Jamie Weaver; Pierre Lao-Sirieix; Inigo Martincorena; Irene Debiram-Beecham; Nicola Grehan; Shona MacRae; Shalini Malhotra; Ahmad Miremadi; Tabitha Thomas; Sarah Galbraith; Lorraine Petersen; Stephen D. Preston; David Gilligan; Andrew Hindmarsh; Richard H. Hardwick; Michael R. Stratton; David C. Wedge; Rebecca C. Fitzgerald
    更新日期:2020-01-06
  • The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins
    Nat. Genet. (IF 25.455) Pub Date : 2020-01-06
    Kushal Suryamohan; Sajesh P. Krishnankutty; Joseph Guillory; Matthew Jevit; Markus S. Schröder; Meng Wu; Boney Kuriakose; Oommen K. Mathew; Rajadurai C. Perumal; Ivan Koludarov; Leonard D. Goldstein; Kate Senger; Mandumpala Davis Dixon; Dinesh Velayutham; Derek Vargas; Subhra Chaudhuri; Megha Muraleedharan; Ridhi Goel; Ying-Jiun J. Chen; Aakrosh Ratan; Peter Liu; Brendan Faherty; Guillermo de la Rosa; Hiroki Shibata; Miriam Baca; Meredith Sagolla; James Ziai; Gus A. Wright; Domagoj Vucic; Sangeetha Mohan; Aju Antony; Jeremy Stinson; Donald S. Kirkpatrick; Rami N. Hannoush; Steffen Durinck; Zora Modrusan; Eric W. Stawiski; Kristen Wiley; Terje Raudsepp; R. Manjunatha Kini; Arun Zachariah; Somasekar Seshagiri
    更新日期:2020-01-06
  • 更新日期:2019-12-23
  • m 6 A RNA modification as a new player in R-loop regulation
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-23
    Aline Marnef; Gaëlle Legube
    更新日期:2019-12-23
  • A call for global action for rare diseases in Africa
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-23
    Gareth S. Baynam; Stephen Groft; Francois H. van der Westhuizen; Safiyya D. Gassman; Kelly du Plessis; Emily P. Coles; Eda Selebatso; Moses Selebatso; Boikobo Gaobinelwe; Tebogo Selebatso; Dipesalema Joel; Virginia A. Llera; Barend C. Vorster; Barbara Wuebbels; Benjamin Djoudalbaye; Christopher P. Austin; Judit Kumuthini; John Forman; Petra Kaufmann; James Chipeta; Désirée Gavhed; Annika Larsson; Maja Stojiljkovic; Ann Nordgren; Emilio J. A. Roldan; Domenica Taruscio; Durhane Wong-Rieger; Kristen Nowak; Gemma A. Bilkey; Simon Easteal; Sarah Bowdin; Juergen K. V. Reichardt; Sergi Beltran; Kenjiro Kosaki; Clara D. M. van Karnebeek; Mengchun Gong; Zhang Shuyang; Ruty Mehrian-Shai; David R. Adams; Ratna D. Puri; Feng Zhang; Nicholas Pachter; Maximilian Muenke; Christoffer Nellaker; William A. Gahl; Helene Cederroth; Stephanie Broley; Maryke Schoonen; Kym M. Boycott; Manuel Posada
    更新日期:2019-12-23
  • Identifying cross-disease components of genetic risk across hospital data in the UK Biobank
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-23
    Adrian Cortes; Patrick K. Albers; Calliope A. Dendrou; Lars Fugger; Gil McVean
    更新日期:2019-12-23
  • Resequencing of 683 common bean genotypes identifies yield component trait associations across a north–south cline
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-23
    Jing Wu; Lanfen Wang; Junjie Fu; Jibao Chen; Shuhong Wei; Shilong Zhang; Jie Zhang; Yongsheng Tang; Mingli Chen; Jifeng Zhu; Lei Lei; Qinghe Geng; Chunliang Liu; Lei Wu; Xiaoming Li; Xiaoli Wang; Qiang Wang; Zhaoli Wang; Shilai Xing; Haikuan Zhang; Matthew W. Blair; Shumin Wang
    更新日期:2019-12-23
  • Reply to: Revisiting the origin of octoploid strawberry
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Patrick P. Edger; Michael R. McKain; Alan E. Yocca; Steven J. Knapp; Qin Qiao; Ticao Zhang
    更新日期:2019-12-17
  • N 6 -methyladenosine regulates the stability of RNA:DNA hybrids in human cells
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Abdulkadir Abakir; Tom C. Giles; Agnese Cristini; Jeremy M. Foster; Nan Dai; Marta Starczak; Alejandro Rubio-Roldan; Miaomiao Li; Maria Eleftheriou; James Crutchley; Luke Flatt; Lorraine Young; Daniel J. Gaffney; Chris Denning; Bjørn Dalhus; Richard D. Emes; Daniel Gackowski; Ivan R. Corrêa; Jose L. Garcia-Perez; Arne Klungland; Natalia Gromak; Alexey Ruzov
    更新日期:2019-12-17
  • Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Richard P. Koche; Elias Rodriguez-Fos; Konstantin Helmsauer; Martin Burkert; Ian C. MacArthur; Jesper Maag; Rocio Chamorro; Natalia Munoz-Perez; Montserrat Puiggròs; Heathcliff Dorado Garcia; Yi Bei; Claudia Röefzaad; Victor Bardinet; Annabell Szymansky; Annika Winkler; Theresa Thole; Natalie Timme; Katharina Kasack; Steffen Fuchs; Filippos Klironomos; Nina Thiessen; Eric Blanc; Karin Schmelz; Annette Künkele; Patrick Hundsdörfer; Carolina Rosswog; Jessica Theissen; Dieter Beule; Hedwig Deubzer; Sascha Sauer; Joern Toedling; Matthias Fischer; Falk Hertwig; Roland F. Schwarz; Angelika Eggert; David Torrents; Johannes H. Schulte; Anton G. Henssen
    更新日期:2019-12-17
  • Epigenomic analysis of gastrulation identifies a unique chromatin state for primed pluripotency
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Yunlong Xiang; Yu Zhang; Qianhua Xu; Chen Zhou; Bofeng Liu; Zhenhai Du; Ke Zhang; Bingjie Zhang; Xiaoxiao Wang; Srimonta Gayen; Ling Liu; Yao Wang; Yuanyuan Li; Qiujun Wang; Sundeep Kalantry; Lei Li; Wei Xie
    更新日期:2019-12-17
  • Loss of ADAMTS19 causes progressive non-syndromic heart valve disease
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Florian Wünnemann; Asaf Ta-Shma; Christoph Preuss; Severine Leclerc; Patrick Piet van Vliet; Andrea Oneglia; Maryse Thibeault; Emily Nordquist; Joy Lincoln; Franka Scharfenberg; Christoph Becker-Pauly; Philipp Hofmann; Kirstin Hoff; Enrique Audain; Hans-Heiner Kramer; Wojciech Makalowski; Amiram Nir; Sebastian S. Gerety; Matthew Hurles; Johanna Comes; Anne Fournier; Hanna Osinska; Jeffrey Robins; Michel Pucéat; Orly Elpeleg; Marc-Phillip Hitz; Gregor Andelfinger
    更新日期:2019-12-17
  • Revisiting the origin of octoploid strawberry
    Nat. Genet. (IF 25.455) Pub Date : 2019-12-16
    Aaron Liston; Na Wei; Jacob A. Tennessen; Junmin Li; Ming Dong; Tia-Lynn Ashman
    更新日期:2019-12-17
  • WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29
    Barbara A. Scholz, Noriyuki Sumida, Carolina Diettrich Mallet de Lima, Ilyas Chachoua, Mirco Martino, Ilias Tzelepis, Andrej Nikoshkov, Honglei Zhao, Rashid Mehmood, Emmanouil G. Sifakis, Deeksha Bhartiya, Anita Göndör, Rolf Ohlsson
    更新日期:2019-11-30
  • Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29
    Charles P. Fulco, Joseph Nasser, Thouis R. Jones, Glen Munson, Drew T. Bergman, Vidya Subramanian, Sharon R. Grossman, Rockwell Anyoha, Benjamin R. Doughty, Tejal A. Patwardhan, Tung H. Nguyen, Michael Kane, Elizabeth M. Perez, Neva C. Durand, Caleb A. Lareau, Elena K. Stamenova, Erez Lieberman Aiden, Eric S. Lander, Jesse M. Engreitz
    更新日期:2019-11-30
  • Mapping and predicting gene–enhancer interactions
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29
    Daniel J. Gaffney
    更新日期:2019-11-30
  • Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29
    Berkley E. Gryder, Silvia Pomella, Carly Sayers, Xiaoli S. Wu, Young Song, Anna M. Chiarella, Sukriti Bagchi, Hsien-Chao Chou, Ranu S. Sinniah, Ashley Walton, Xinyu Wen, Rossella Rota, Nathaniel A. Hathaway, Keji Zhao, Jiji Chen, Christopher R. Vakoc, Jack F. Shern, Benjamin Z. Stanton, Javed Khan
    更新日期:2019-11-30
  • A year in genetics
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29

    As the year comes to a close and we start to look ahead to 2020, we thought that we would highlight some of our favorite Nature Genetics papers from 2019. This snapshot also captures some of the topics and themes in genetics that we are most excited to see develop in the near future.

    更新日期:2019-11-30
  • Neuronal impact of patient-specific aberrant NRXN1α splicing
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-29
    Erin Flaherty, Shijia Zhu, Natalie Barretto, Esther Cheng, P. J. Michael Deans, Michael B. Fernando, Nadine Schrode, Nancy Francoeur, Alesia Antoine, Khaled Alganem, Madeline Halpern, Gintaras Deikus, Hardik Shah, Megan Fitzgerald, Ian Ladran, Peter Gochman, Judith Rapoport, Nadejda M. Tsankova, Robert McCullumsmith, Gabriel E. Hoffman, Robert Sebra, Gang Fang, Kristen J. Brennand
    更新日期:2019-11-30
  • Lack of detectable neoantigen depletion signals in the untreated cancer genome
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-25
    Jimmy Van den Eynden, Alejandro Jiménez-Sánchez, Martin L. Miller, Erik Larsson

    Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface by HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. On the basis of HLA affinity predictions, we annotated the human genome for its translatability to HLA binding peptides and screened for reduced single nucleotide substitution rates in large genomic data sets from untreated cancers. Apparent neoantigen depletion signals become negligible when taking into consideration trinucleotide-based mutational signatures, owing to lack of power or to efficient immune evasion mechanisms that are active early during tumor evolution.

    更新日期:2019-11-26
  • Returning incidental findings in African genomics research
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-25
    Ambroise Wonkam, Jantina de Vries

    Ancestral and geographical issues underlie the need to develop Africa-specific guidelines for the return of genomics research results in Africa. In this Commentary, we outline the challenges that will inform policies and practices in the future.

    更新日期:2019-11-26
  • A resource-efficient tool for mixed model association analysis of large-scale data
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-25
    Longda Jiang, Zhili Zheng, Ting Qi, Kathryn E. Kemper, Naomi R. Wray, Peter M. Visscher, Jian Yang

    The genome-wide association study (GWAS) has been widely used as an experimental design to detect associations between genetic variants and a phenotype. Two major confounding factors, population stratification and relatedness, could potentially lead to inflated GWAS test statistics and hence to spurious associations. Mixed linear model (MLM)-based approaches can be used to account for sample structure. However, genome-wide association (GWA) analyses in biobank samples such as the UK Biobank (UKB) often exceed the capability of most existing MLM-based tools especially if the number of traits is large. Here, we develop an MLM-based tool (fastGWA) that controls for population stratification by principal components and for relatedness by a sparse genetic relationship matrix for GWA analyses of biobank-scale data. We demonstrate by extensive simulations that fastGWA is reliable, robust and highly resource-efficient. We then apply fastGWA to 2,173 traits on array-genotyped and imputed samples from 456,422 individuals and to 2,048 traits on whole-exome-sequenced samples from 46,191 individuals in the UKB.

    更新日期:2019-11-26
  • Stalled developmental programs at the root of pediatric brain tumors
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-25
    Selin Jessa, Alexis Blanchet-Cohen, Brian Krug, Maria Vladoiu, Marie Coutelier, Damien Faury, Brice Poreau, Nicolas De Jay, Steven Hébert, Jean Monlong, W. Todd Farmer, Laura K. Donovan, Yixing Hu, Melissa K. McConechy, Florence M. G. Cavalli, Leonie G. Mikael, Benjamin Ellezam, Maxime Richer, Andréa Allaire, Alexander G. Weil, Jeffrey Atkinson, Jean-Pierre Farmer, Roy W. R. Dudley, Valerie Larouche, Louis Crevier, Steffen Albrecht, Mariella G. Filbin, Hervé Sartelet, Pierre-Eric Lutz, Corina Nagy, Gustavo Turecki, Santiago Costantino, Peter B. Dirks, Keith K. Murai, Guillaume Bourque, Jiannis Ragoussis, Livia Garzia, Michael D. Taylor, Nada Jabado, Claudia L. Kleinman

    Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

    更新日期:2019-11-26
  • The mutational footprints of cancer therapies
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-18
    Oriol Pich, Ferran Muiños, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez, Nuria Lopez-Bigas
    更新日期:2019-11-18
  • Comparative genetic architectures of schizophrenia in East Asian and European populations
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-18
    Max Lam, Chia-Yen Chen, Zhiqiang Li, Alicia R. Martin, Julien Bryois, Xixian Ma, Helena Gaspar, Masashi Ikeda, Beben Benyamin, Brielin C. Brown, Ruize Liu, Wei Zhou, Lili Guan, Yoichiro Kamatani, Sung-Wan Kim, Michiaki Kubo, Agung A. A. A. Kusumawardhani, Chih-Min Liu, Hong Ma, Sathish Periyasamy, Atsushi Takahashi, Zhida Xu, Hao Yu, Feng Zhu, Wei J. Chen, Stephen Faraone, Stephen J. Glatt, Lin He, Steven E. Hyman, Hai-Gwo Hwu, Steven A. McCarroll, Benjamin M. Neale, Pamela Sklar, Dieter B. Wildenauer, Xin Yu, Dai Zhang, Bryan J. Mowry, Jimmy Lee, Peter Holmans, Shuhua Xu, Patrick F. Sullivan, Stephan Ripke, Michael C. O’Donovan, Mark J. Daly, Shengying Qin, Pak Sham, Nakao Iwata, Kyung S. Hong, Sibylle G. Schwab, Weihua Yue, Ming Tsuang, Jianjun Liu, Xiancang Ma, René S. Kahn, Yongyong Shi, Hailiang Huang
    更新日期:2019-11-18
  • Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-18
    Angels Almenar-Queralt, Daria Merkurjev, Hong Sook Kim, Michael Navarro, Qi Ma, Rodrigo S. Chaves, Catarina Allegue, Shawn P. Driscoll, Andrew G. Chen, Bridget Kohlnhofer, Lauren K. Fong, Grace Woodruff, Carlos Mackintosh, Dasa Bohaciakova, Marian Hruska-Plochan, Takahiro Tadokoro, Jessica E. Young, Nady El Hajj, Marcus Dittrich, Martin Marsala, Lawrence S. B. Goldstein, Ivan Garcia-Bassets
    更新日期:2019-11-18
  • Resequencing of 414 cultivated and wild watermelon accessions identifies selection for fruit quality traits
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Shaogui Guo, Shengjie Zhao, Honghe Sun, Xin Wang, Shan Wu, Tao Lin, Yi Ren, Lei Gao, Yun Deng, Jie Zhang, Xuqiang Lu, Haiying Zhang, Jianli Shang, Guoyi Gong, Changlong Wen, Nan He, Shouwei Tian, Maoying Li, Junpu Liu, Yanping Wang, Yingchun Zhu, Robert Jarret, Amnon Levi, Xingping Zhang, Sanwen Huang, Zhangjun Fei, Wenge Liu, Yong Xu
    更新日期:2019-11-01
  • Loss of ZnT8 function protects against diabetes by enhanced insulin secretion
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Om Prakash Dwivedi, Mikko Lehtovirta, Benoit Hastoy, Vikash Chandra, Nicole A. J. Krentz, Sandra Kleiner, Deepak Jain, Ann-Marie Richard, Fernando Abaitua, Nicola L. Beer, Antje Grotz, Rashmi B. Prasad, Ola Hansson, Emma Ahlqvist, Ulrika Krus, Isabella Artner, Anu Suoranta, Daniel Gomez, Aris Baras, Benoite Champon, Anthony J. Payne, Daniela Moralli, Soren K. Thomsen, Philipp Kramer, Ioannis Spiliotis, Reshma Ramracheya, Pauline Chabosseau, Andria Theodoulou, Rebecca Cheung, Martijn van de Bunt, Jason Flannick, Maddalena Trombetta, Enzo Bonora, Claes B. Wolheim, Leena Sarelin, Riccardo C. Bonadonna, Patrik Rorsman, Benjamin Davies, Julia Brosnan, Mark I. McCarthy, Timo Otonkoski, Jens O. Lagerstedt, Guy A. Rutter, Jesper Gromada, Anna L. Gloyn, Tiinamaija Tuomi, Leif Groop
    更新日期:2019-11-01
  • PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Antonio Rueda Martin, Eleanor Williams, Rebecca E. Foulger, Sarah Leigh, Louise C. Daugherty, Olivia Niblock, Ivone U. S. Leong, Katherine R. Smith, Oleg Gerasimenko, Eik Haraldsdottir, Ellen Thomas, Richard H. Scott, Emma Baple, Arianna Tucci, Helen Brittain, Anna de Burca, Kristina Ibañez, Dalia Kasperaviciute, Damian Smedley, Mark Caulfield, Augusto Rendon, Ellen M. McDonagh
    更新日期:2019-11-01
  • Genome-wide association analysis of 19,629 individuals identifies variants influencing regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Bingxin Zhao, Tianyou Luo, Tengfei Li, Yun Li, Jingwen Zhang, Yue Shan, Xifeng Wang, Liuqing Yang, Fan Zhou, Ziliang Zhu, Hongtu Zhu
    更新日期:2019-11-01
  • Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Derek Klarin, Emma Busenkell, Renae Judy, Julie Lynch, Michael Levin, Jeffery Haessler, Krishna Aragam, Mark Chaffin, Mary Haas, Sara Lindström, Themistocles L. Assimes, Jie Huang, Kyung Min Lee, Qing Shao, Jennifer E. Huffman, Christopher Kabrhel, Yunfeng Huang, Yan V. Sun, Marijana Vujkovic, Danish Saleheen, Donald R. Miller, Peter Reaven, Scott DuVall, William E. Boden, Saiju Pyarajan, Alex P. Reiner, David-Alexandre Trégouët, Peter Henke, Charles Kooperberg, J. Michael Gaziano, John Concato, Daniel J. Rader, Kelly Cho, Kyong-Mi Chang, Peter W. F. Wilson, Nicholas L. Smith, Christopher J. O’Donnell, Philip S. Tsao, Sekar Kathiresan, Andrea Obi, Scott M. Damrauer, Pradeep Natarajan
    更新日期:2019-11-01
  • Sweet sequencing
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01

    Popular crop plants have been bred and selected for desirable taste and color traits. Genomic approaches are increasingly being used to provide insights into the origins, evolution and biology of our favorite foods. Large-scale sequencing efforts have brought agriculture genomics into the big-data era, leading to sweet rewards.

    更新日期:2019-11-01
  • The impact of short tandem repeat variation on gene expression
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Stephanie Feupe Fotsing, Jonathan Margoliash, Catherine Wang, Shubham Saini, Richard Yanicky, Sharona Shleizer-Burko, Alon Goren, Melissa Gymrek
    更新日期:2019-11-01
  • Sweet genes in melon and watermelon
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Murukarthick Jayakodi, Mona Schreiber, Martin Mascher
    更新日期:2019-11-01
  • The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Mireia Ramos-Rodríguez, Helena Raurell-Vila, Maikel L. Colli, Maria Inês Alvelos, Marc Subirana-Granés, Jonàs Juan-Mateu, Richard Norris, Jean-Valery Turatsinze, Ernesto S. Nakayasu, Bobbie-Jo M. Webb-Robertson, Jamie R. J. Inshaw, Piero Marchetti, Lorenzo Piemonti, Manel Esteller, John A. Todd, Thomas O. Metz, Décio L. Eizirik, Lorenzo Pasquali
    更新日期:2019-11-01
  • A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits
    Nat. Genet. (IF 25.455) Pub Date : 2019-11-01
    Guangwei Zhao, Qun Lian, Zhonghua Zhang, Qiushi Fu, Yuhua He, Shuangwu Ma, Valentino Ruggieri, Antonio J. Monforte, Pingyong Wang, Irene Julca, Huaisong Wang, Junpu Liu, Yong Xu, Runze Wang, Jiabing Ji, Zhihong Xu, Weihu Kong, Yang Zhong, Jianli Shang, Lara Pereira, Jason Argyris, Jian Zhang, Carlos Mayobre, Marta Pujol, Elad Oren, Diandian Ou, Jiming Wang, Dexi Sun, Shengjie Zhao, Yingchun Zhu, Na Li, Nurit Katzir, Amit Gur, Catherine Dogimont, Hanno Schaefer, Wei Fan, Abdelhafid Bendahmane, Zhangjun Fei, Michel Pitrat, Toni Gabaldón, Tao Lin, Jordi Garcia-Mas, Yongyang Xu, Sanwen Huang
    更新日期:2019-11-01
  • Regulating mRNA complexity in the mammalian brain.
    Nat. Genet. (IF 25.455) Pub Date : 2011-08-19
    Thomas A Cooper

    更新日期:2019-11-01
  • Genetics of cardiac repolarization.
    Nat. Genet. (IF 25.455) Pub Date : 2009-04-02
    Svati H Shah,Geoffrey S Pitt

    Prolongation of the electrocardiographic QT interval, a measure of cardiac repolarization, is associated with arrhythmogenic disorders and is a risk factor for sudden cardiac death. Two genome-wide association studies (GWAS) of variation in the QT interval in population-based cohorts now report association with variants in a subset of ion channel genes and other new associations.

    更新日期:2019-11-01
  • BMP6 orchestrates iron metabolism.
    Nat. Genet. (IF 25.455) Pub Date : 2009-04-02
    Clara Camaschella

    The small liver peptide hepcidin is a major regulator of systemic iron homeostasis in mammals, adapting iron absorption to the body's demands. Two new studies now identify BMP6 as the key endogenous regulator of hepcidin.

    更新日期:2019-11-01
  • Somatic and germline genetics at the JAK2 locus.
    Nat. Genet. (IF 25.455) Pub Date : 2009-04-02
    Peter J Campbell

    Myeloproliferative neoplasms are hematological malignancies frequently associated with somatically acquired mutation of the JAK2 gene. A new study shows that these mutations are preferentially found within a particular inherited JAK2 haplotype, implying the existence of a strong, but uncharacterized, interaction between somatic and germline genetics at this locus.

    更新日期:2019-11-01
  • Common deletion polymorphisms in the human genome.
    Nat. Genet. (IF 25.455) Pub Date : 2006-02-10
    Steven A McCarroll,Tracy N Hadnott,George H Perry,Pardis C Sabeti,Michael C Zody,Jeffrey C Barrett,Stephanie Dallaire,Stacey B Gabriel,Charles Lee,Mark J Daly,David M Altshuler,

    The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.

    更新日期:2019-11-01
  • A road map for efficient and reliable human genome epidemiology.
    Nat. Genet. (IF 25.455) Pub Date : 2006-02-10
    John P A Ioannidis,Marta Gwinn,Julian Little,Julian P T Higgins,Jonine L Bernstein,Paolo Boffetta,Melissa Bondy,Molly S Bray,Paul E Brenchley,Patricia A Buffler,Juan Pablo Casas,Anand Chokkalingam,John Danesh,George Davey Smith,Siobhan Dolan,Ross Duncan,Nelleke A Gruis,Patricia Hartge,Mia Hashibe,David J Hunter,Marjo-Riitta Jarvelin,Beatrice Malmer,Demetrius M Maraganore,Julia A Newton-Bishop,Thomas R O'Brien,Gloria Petersen,Elio Riboli,Georgia Salanti,Daniela Seminara,Liam Smeeth,Emanuela Taioli,Nic Timpson,Andre G Uitterlinden,Paolo Vineis,Nick Wareham,Deborah M Winn,Ron Zimmern,Muin J Khoury,

    Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

    更新日期:2019-11-01
  • Gene therapy restores vision in a canine model of childhood blindness.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    G M Acland,G D Aguirre,J Ray,Q Zhang,T S Aleman,A V Cideciyan,S E Pearce-Kelling,V Anand,Y Zeng,A M Maguire,S G Jacobson,W W Hauswirth,J Bennett

    The relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (RPE) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. The molecular bases for both primary photoreceptor and RPE diseases that cause blindness have been identified. Gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases, but efficacy of gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported. Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA). LCA causes near total blindness in infancy and can result from mutations in RPE65 (LCA, type II; MIM 180069 and 204100). A naturally occurring animal model, the RPE65-/- dog, suffers from early and severe visual impairment similar to that seen in human LCA. We used a recombinant adeno-associated virus (AAV) carrying wild-type RPE65 (AAV-RPE65) to test the efficacy of gene therapy in this model. Our results indicate that visual function was restored in this large animal model of childhood blindness.

    更新日期:2019-11-01
  • A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    T Laitinen,M J Daly,J D Rioux,P Kauppi,C Laprise,T Petäys,T Green,M Cargill,T Haahtela,E S Lander,L A Laitinen,T J Hudson,J Kere

    The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.

    更新日期:2019-11-01
  • Haploinsufficiency of protamine-1 or -2 causes infertility in mice.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    C Cho,W D Willis,E H Goulding,H Jung-Ha,Y C Choi,N B Hecht,E M Eddy

    Protamines are the major DNA-binding proteins in the nucleus of sperm in most vertebrates and package the DNA in a volume less than 5% of a somatic cell nucleus. Many mammals have one protamine, but a few species, including humans and mice, have two. Here we use gene targeting to determine if the second protamine provides redundancy to an essential process, or if both protamines are necessary. We disrupted the coding sequence of one allele of either Prm1 or Prm2 in embryonic stem (ES) cells derived from 129-strain mice, and injected them into blastocysts from C57BL/6-strain mice. Male chimeras produced 129-genotype sperm with disrupted Prm1 or Prm2 alleles, but failed to sire offspring carrying the 129 genome. We also found that a decrease in the amount of either protamine disrupts nuclear formation, processing of protamine-2 and normal sperm function. Our studies show that both protamines are essential and that haploinsufficiency caused by a mutation in one allele of Prm1 or Prm2 prevents genetic transmission of both mutant and wild-type alleles.

    更新日期:2019-11-01
  • Transposable B2 SINE elements can provide mobile RNA polymerase II promoters.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    O Ferrigno,T Virolle,Z Djabari,J P Ortonne,R J White,D Aberdam

    Short interspersed elements (SINEs) are highly abundant components of mammalian genomes that are propagated by retrotransposition. SINEs are recognized as a causal agent of human disease and must also have had a profound influence in shaping eukaryotic genomes. The B2 SINE family constitutes approximately 0.7% of total mouse genomic DNA (ref. 2) and is also found at low abundance in humans. It resembles the Alu family in several respects, such as its mechanism of propagation. B2 SINEs are derived from tRNA and are transcribed by RNA polymerase (pol) III to generate short transcripts that are not translated. We find here, however, that one B2 SINE also carries an active pol II promoter located outside the tRNA region. Indeed, a B2 element is responsible for the production of a mouse Lama3 transcript. The B2 pol II promoters can be bound and stimulated by the transcription factor USF (for upstream stimulatory factor), as shown by transient transfection experiments. Moreover, this pol II activity does not preclude the pol III transcription necessary for retrotransposition. Dispersal of B2 SINEs by retrotransposition may therefore have provided numerous opportunities for creating regulated pol II transcription at novel genomic sites. This mechanism may have allowed the evolution of new transcription units and new genes.

    更新日期:2019-11-01
  • Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    T Lübke,T Marquardt,A Etzioni,E Hartmann,K von Figura,C Körner

    Congenital disorders of glycosylation (CDG) comprise a rapidly growing group of inherited disorders in which glycosylation of glycoproteins is defective due to mutations in genes required for the assembly of lipid-linked oligosaccharides, their transfer to nascent glycoproteins (CDG-I) or the processing of protein-bound glycans (CDG-II). Previously' a defect in the GDP-fucose import into the lumen of the Golgi was identified in a person with CDG (A.C.) with a general deficiency of fucosyl residues in glycoproteins. This patient presents the clinical features of leukocyte adhesion deficiency type II (LAD II) including mental retardation, short stature, facial stigmata, and recurrent bacterial peripheral infections with persistently elevated peripheral leukocytes. Using a fucose-specific, lectin-staining procedure for detection of fucosylated glycoproteins and a retroviral cDNA library, we isolated a cDNA complementing the fucosylation defect in the patient's fibroblasts. The cDNA encodes a highly hydrophobic protein of 364 amino acids with multiple putative transmembrane domains. Restoration of GDP-fucose import activity in Golgi-enriched vesicles from the patient's fibroblasts verified the GDP-fucose transporter activity of this protein. We identified two missense mutations in the GDP-fucose transporter cDNA of patient A.C. and of two other people with LAD II. Thus complementation cloning allowed us to identify the human GDP-fucose transporter cDNA and GDP-fucose transporter deficiency as a cause for a new type of CDG. Following the recent recommendations for the nomenclature for CDG, this new type is classified as CDG-IIc (formerly LAD II).

    更新日期:2019-11-01
  • The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    K Lühn,M K Wild,M Eckhardt,R Gerardy-Schahn,D Vestweber

    Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation. No deficiency in fucosyltransferase activities or in the activities of enzymes involved in GDP-fucose biosynthesis has been found. Instead, the transport of GDP-fucose into isolated Golgi vesicles of LAD II cells appeared to be reduced. To identify the gene mutated in LAD II, we cloned 12 cDNAs from Caenorhabditis elegans, encoding multi-spanning transmembrane proteins with homology to known nucleotide sugar transporters, and transfected them into fibroblasts from an LAD II patient. One of these clones re-established expression of fucosylated glycoconjugates with high efficiency and allowed us to identify a human homolog with 55% identity, which also directed re-expression of fucosylated glycoconjugates. Both proteins were localized to the Golgi. The corresponding endogenous protein in LAD II cells had an R147C amino acid change in the conserved fourth transmembrane region. Overexpression of this mutant protein in cells from a patient with LAD II did not rescue fucosylation, demonstrating that the point mutation affected the activity of the protein. Thus, we have identified the first putative GDP-fucose transporter, which has been highly conserved throughout evolution. A point mutation in its gene is responsible for the disease in this patient with LAD II.

    更新日期:2019-11-01
  • Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    H Fares,I Greenwald

    Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a lysosomal storage disease that results in severe developmental neuropathology. Unlike other lysosomal storage diseases, MLIV is not associated with a lack of lysosomal hydrolases; instead, MLIV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. Here we report the identification of a loss-of-function mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup-5, and show that this mutation results in an enhanced rate of uptake of fluid-phase markers, decreased degradation of endocytosed protein and accumulation of large vacuoles. Overexpression of cup-5(+) causes the opposite phenotype, indicating that cup-5 activity controls aspects of endocytosis. Studies in model organisms such as C. elegans have helped illuminate fundamental mechanisms involved in normal cellular function and human disease; thus the C. elegans cup-5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds.

    更新日期:2019-11-01
  • Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac.
    Nat. Genet. (IF 25.455) Pub Date : 2001-04-28
    M Max,Y G Shanker,L Huang,M Rong,Z Liu,F Campagne,H Weinstein,S Damak,R F Margolskee

    The ability to taste the sweetness of carbohydrate-rich foodstuffs has a critical role in the nutritional status of humans. Although several components of bitter transduction pathways have been identified, the receptors and other sweet transduction elements remain unknown. The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7-9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners. To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human genome syntenous to the region of Sac in mouse. From this search, we identified a likely candidate: T1R3, a previously unknown G protein-coupled receptor (GPCR) and the only GPCR in this region. Mouse Tas1r3 (encoding T1r3) maps to within 20,000 bp of the marker closest to Sac (ref. 9) and, like human TAS1R3, is expressed selectively in taste receptor cells. By comparing the sequence of Tas1r3 from several independently derived strains of mice, we identified a specific polymorphism that assorts between taster and non-taster strains. According to models of its structure, T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization.

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
加州大学洛杉矶分校
上海纽约大学William Glover
南开大学化学院周其林
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug