Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium.
Stephen D.M. Brown,Mark W. Moore +1 more
TLDR
It is salutary to reflect that the authors remain remarkably ignorant of the function of most genes in the mammalian genome, clearly illustrated from the outputs of genome-wide.Abstract:
Nearly 10 years after the completion of the human genome project, and the report of a complete sequence of the mouse genome, it is salutary to reflect that we remain remarkably ignorant of the function of most genes in the mammalian genome. This is clearly illustrated from the outputs of genome-wideread more
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A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
Lars G. Fritsche,Wilmar Igl,Jessica N. Cooke Bailey,Felix Grassmann,Sebanti Sengupta,Jennifer L. Bragg-Gresham,Kathryn P. Burdon,Scott J. Hebbring,Cindy Wen,Mathias Gorski,Ivana K. Kim,David Cho,Donald J. Zack,Donald J. Zack,Eric H. Souied,Hendrik P. N. Scholl,Hendrik P. N. Scholl,Elisa Bala,Kristine ELee,David J. Hunter,Rebecca J. Sardell,Paul Mitchell,Joanna E. Merriam,Valentina Cipriani,Valentina Cipriani,Joshua D. Hoffman,Tina Schick,Yara T. E. Lechanteur,Robyn H. Guymer,Matthew P. Johnson,Yingda Jiang,Chloe M. Stanton,Gabri'lle H.S. Buitendijk,Xiaowei Zhan,Xiaowei Zhan,Alan M. Kwong,Alexis Boleda,Matthew Brooks,Linn Gieser,Rinki Ratnapriya,Kari Branham,Johanna R. Foerster,John R. Heckenlively,Mohammad Othman,Brendan J. Vote,Helena Liang,Emmanuelle Souzeau,Ian L. McAllister,Timothy Isaacs,Janette Hall,Stewart Lake,David A. Mackey,David A. Mackey,David A. Mackey,Ian J. Constable,Jamie E Craig,Terrie Kitchner,Zhenglin Yang,Zhenglin Yang,Zhiguang Su,Hongrong Luo,Daniel Chen,Hong Ouyang,Ken Flagg,Danni Lin,Guanping Mao,Henry Ferreyra,Klaus Stark,Claudia N von Strachwitz,Armin Wolf,Caroline Brandl,G. Rudolph,Matthias Olden,Margaux A. Morrison,Denise J. Morgan,Matthew Schu,Jeeyun Ahn,Giuliana Silvestri,Evangelia E. Tsironi,Kyu Hyung Park,Lindsay A. Farrer,Anton Orlin,Alexander J. Brucker,Mingyao Li,Christine A. Curcio,Saddek Mohand-Sa'd,José-Alain Sahel,Isabelle Audo,Mustapha Benchaboune,Angela J. Cree,Christina A Rennie,S. V. Goverdhan,Michelle Grunin,Shira Hagbi-Levi,Peter A. Campochiaro,Nicholas Katsanis,Frank G. Holz,Frédéric Blond,Frédéric Blond,Frédéric Blond,Hél'ne Blanché,Jean Fran ois Deleuze,Robert P. Igo,Barbara Truitt,Neal S. Peachey,Neal S. Peachey,Stacy M. Meuer,Chelsea E. Myers,Emily L. Moore,Ronald Klein,Michael A. Hauser,Eric A. Postel,Monique D. Courtenay,Stephen G. Schwartz,Jaclyn L. Kovach,William K. Scott,Gerald Liew,Ava Grace Tan,Bamini Gopinath,John C. Merriam,R. Theodore Smith,R. Theodore Smith,Jane C. Khan,Jane C. Khan,Jane C. Khan,Humma Shahid,Humma Shahid,Anthony T. Moore,Anthony T. Moore,Anthony T. Moore,J Allie McGrath,Renee Laux,Milam A. Brantley,Anita Agarwal,Lebriz Ersoy,Albert Caramoy,Thomas Langmann,Nicole T.M. Saksens,Eiko Kde Jong,Carel B. Hoyng,Melinda Cain,Andrea J. Richardson,Tammy M. Martin,John Blangero,Daniel E. Weeks,Bal Dhillon,Cornelia M. van Duijn,Kimberly F. Doheny,Jane Romm,Caroline C W Klaver,Caroline Hayward,Michael B. Gorin,Michael L. Klein,Paul N. Baird,Anneke I. den Hollander,Sascha Fauser,John R. WYates,John R. WYates,John R. WYates,Rando Allikmets,Jie Jin Wang,Debra A. Schaumberg,Debra A. Schaumberg,Barbara E.K. Klein,Stephanie A. Hagstrom,Itay Chowers,Andrew J. Lotery,Thierry Léveillard,Thierry Léveillard,Thierry Léveillard,Kang Zhang,Kang Zhang,Murray H. Brilliant,Alex W. Hewitt,Alex W. Hewitt,Alex W. Hewitt,Anand Swaroop,Emily Y. Chew,Margaret A. Pericak-Vance,Margaret M. DeAngelis,Dwight Stambolian,Jonathan L. Haines,Sudha K. Iyengar,Bernhard H. F. Weber,Gon'alo R. Abecasis,Iris M. Heid +185 more
TL;DR: The results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Journal ArticleDOI
Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes
Jacqueline K. White,Anna-Karin Gerdin,Natasha A. Karp,Edward Ryder,Marija Buljan,James Bussell,Jennifer Salisbury,Simon Clare,Neil J. Ingham,Christine Podrini,Richard Houghton,Jeanne Estabel,Joanna Bottomley,David Melvin,David Sunter,Niels C. Adams,David Tannahill,Darren W. Logan,Daniel G. MacArthur,Jonathan Flint,Vinit B. Mahajan,Stephen H. Tsang,Ian M. Smyth,Fiona M. Watt,William C. Skarnes,Gordon Dougan,David J. Adams,Ramiro Ramirez-Solis,Allan Bradley,Karen P. Steel +29 more
TL;DR: A program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits is described and it is found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease.
Journal ArticleDOI
A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains
Michelle Simon,Simon Greenaway,Jacqueline K. White,Helmut Fuchs,Valerie Gailus-Durner,Sara Wells,Tania Sorg,Kim Wong,Elodie Bedu,Elizabeth J. Cartwright,Romain Dacquin,Sophia Djebali,Jeanne Estabel,Jochen Graw,Neil J. Ingham,Ian J. Jackson,Andreas Lengeling,Silvia Mandillo,Jacqueline Marvel,Hamid Meziane,Frédéric Preitner,Oliver Puk,Michel Roux,David J. Adams,Sarah Atkins,Abdel Ayadi,Lore Becker,Andrew Blake,Debra Brooker,Heather Cater,Marie-France Champy,Roy Combe,Petr Danecek,Armida Di Fenza,Hilary Gates,Anna-Karin Gerdin,Elisabetta Golini,John M. Hancock,Wolfgang Hans,Sabine M. Hölter,Tertius Hough,Pierre Jurdic,Thomas M. Keane,Hugh P. Morgan,Werner Müller,Frauke Neff,George Nicholson,Bastian Pasche,Laura-Anne Roberson,Jan Rozman,Mark Sanderson,Luis Santos,Mohammed Selloum,Carl Shannon,Anne Southwell,Glauco P. Tocchini-Valentini,Valerie E. Vancollie,Henrik Westerberg,Wolfgang Wurst,Min Zi,Binnaz Yalcin,Binnaz Yalcin,Ramiro Ramirez-Solis,Karen P. Steel,Ann-Marie Mallon,Martin Hrabě de Angelis,Yann Herault,Steve D.M. Brown +67 more
TL;DR: Comparison of C57BL/6J and C57bl/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains.
Journal ArticleDOI
Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.
Danish Saleheen,Pradeep Natarajan,Pradeep Natarajan,Irina M. Armean,Irina M. Armean,Wei Zhao,Asif Rasheed,Sumeet A. Khetarpal,Hong-Hee Won,Konrad J. Karczewski,Konrad J. Karczewski,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Kaitlin E. Samocha,Kaitlin E. Samocha,Benjamin Weisburd,Benjamin Weisburd,Namrata Gupta,Mozzam Zaidi,Maria Samuel,Atif Imran,Shahid Abbas,Faisal Majeed,Madiha Ishaq,Saba Akhtar,Kevin Trindade,Megan L. Mucksavage,Nadeem Qamar,Khan Shah Zaman,Zia Yaqoob,Tahir Saghir,Syed Nadeem Hasan Rizvi,Anis Memon,Nadeem Hayat Mallick,Mohammad Ishaq,Syed Zahed Rasheed,Fazal-ur-Rehman Memon,Khalid Mahmood,Naveeduddin Ahmed,Ron Do,Ronald M. Krauss,Daniel G. MacArthur,Daniel G. MacArthur,Stacey Gabriel,Eric S. Lander,Mark J. Daly,Mark J. Daly,Philippe M. Frossard,John Danesh,John Danesh,Daniel J. Rader,Sekar Kathiresan,Sekar Kathiresan +53 more
TL;DR: Overall, these observations provide a roadmap for a ‘human knockout project’, a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.
Journal ArticleDOI
The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data
Gautier Koscielny,Gagarine Yaikhom,Vivek Iyer,Terrence F. Meehan,Hugh Morgan,Julian Atienza-Herrero,Andrew Blake,Chao-Kung Chen,Richard Easty,Armida Di Fenza,Tanja Fiegel,Mark Grifiths,Alan Horne,Natasha A. Karp,Natalja Kurbatova,Jeremy Mason,Peter Matthews,Darren J. Oakley,Asfand Qazi,Jack Regnart,Ahmad Retha,Luis Santos,Duncan Sneddon,Jonathan Warren,Henrik Westerberg,Robert J. Wilson,David Melvin,Damian Smedley,Steve D.M. Brown,Paul Flicek,William C. Skarnes,Ann-Marie Mallon,Helen Parkinson +32 more
TL;DR: The IMPC web portal provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data, and will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.
References
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Journal ArticleDOI
A conditional knockout resource for the genome-wide study of mouse gene function.
William C. Skarnes,Barry Rosen,Anthony P. West,Manousos Koutsourakis,Wendy Bushell,Vivek Iyer,Alejandro O. Mujica,Alejandro O. Mujica,Mark G. Thomas,Jennifer Harrow,Tony Cox,David A. Jackson,Jessica Severin,Jessica Severin,Patrick J. Biggs,Patrick J. Biggs,Jun Fu,Michael Nefedov,Pieter J. de Jong,A. Francis Stewart,Allan Bradley +20 more
TL;DR: High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.
Journal ArticleDOI
The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse
TL;DR: Improvements to MGD include expanded genome feature classifications, inclusion of new mutant allele sets and phenotype associations and extensions of GO to include new relationships and a new stream of annotations via phylogenetic-based approaches.
Journal ArticleDOI
Understanding Mammalian Genetic Systems: The Challenge of Phenotyping in the Mouse
TL;DR: The scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms and it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome.
Journal ArticleDOI
Technical approaches for mouse models of human disease.
TL;DR: This poster review outlines the major genome manipulations available in the mouse that are used to understand human disease: natural variation, reverse genetics, forward genetics, transgenics and transposons.
Journal ArticleDOI
Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice.
TL;DR: Evidence is presented for the unique contribution that Histopathology can make to a large-scale phenotyping effort, using examples from past and current programmes at Lexicon Pharmaceuticals and The Jackson Laboratory, and the role of histopathology analysis in high-throughput Phenotyping pipelines is critically assessed.
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