Journal ArticleDOI
Structural Variation in the Human Genome and its Role in Disease
TLDR
The discovery of submicroscopic copy-number variations (CNVs) present in the authors' genomes has changed dramatically their perspective on DNA structural variation and disease and it is now thought that CNVs encompass more total nucleotides and arise more frequently than SNPs.Abstract:
During the last quarter of the twentieth century, our knowledge about human genetic variation was limited mainly to the heterochromatin polymorphisms, large enough to be visible in the light microscope, and the single nucleotide polymorphisms (SNPs) identified by traditional PCR-based DNA sequencing. In the past five years, the rapid development and expanded use of microarray technologies, including oligonucleotide array comparative genomic hybridization and SNP genotyping arrays, as well as next-generation sequencing with “paired-end” methods, has enabled a whole-genome analysis with essentially unlimited resolution. The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA structural variation and disease. It is now thought that CNVs encompass more total nucleotides and arise more frequently than SNPs. CNVs, to a larger extent than SNPs, have been shown to be responsible for human evolution, genetic diversity between individuals,...read more
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Coming of age: ten years of next-generation sequencing technologies
TL;DR: These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.
Journal ArticleDOI
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
S. Hong Lee,Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Stephen V. Faraone,Shaun Purcell,Shaun Purcell,Shaun Purcell,Roy H. Perlis,Roy H. Perlis,Bryan J. Mowry,Bryan J. Mowry,Anita Thapar,Michael E. Goddard,John S. Witte,Devin Absher,Ingrid Agartz,Huda Akil,Farooq Amin,Ole A. Andreassen,Adebayo Anjorin,Richard Anney,Verneri Anttila,Dan E. Arking,Philip Asherson,Maria Helena Pinto de Azevedo,Lena Backlund,Judith A. Badner,Anthony J. Bailey,Tobias Banaschewski,Jack D. Barchas,Michael R. Barnes,Thomas B. Barrett,Nicholas Bass,Agatino Battaglia,Michael Bauer,Mònica Bayés,Frank Bellivier,Sarah E. Bergen,Sarah E. Bergen,Sarah E. Bergen,Wade H. Berrettini,Catalina Betancur,Catalina Betancur,Catalina Betancur,Thomas Bettecken,Joseph Biederman,Elisabeth B. Binder,Donald W. Black,Douglas Blackwood,Cinnamon S. Bloss,Michael Boehnke,Dorret I. Boomsma,Gerome Breen,Gerome Breen,René Breuer,Richard Bruggeman,Paul Cormican,Nancy G. Buccola,Jan K. Buitelaar,William E. Bunney,Joseph D. Buxbaum,William Byerley,Enda M. Byrne,Sian Caesar,Wiepke Cahn,Rita M. Cantor,Miguel Casas,Aravinda Chakravarti,Kimberly Chambert,Khalid Choudhury,Sven Cichon,Sven Cichon,C. Robert Cloninger,David A. Collier,Edwin H. Cook,Hilary Coon,Bru Cormand,Aiden Corvin,William Coryell,David Craig,Ian W. Craig,Jennifer Crosbie,Michael L. Cuccaro,David Curtis,Darina Czamara,Susmita Datta,Geraldine Dawson,Richard O. Day,Eco J. C. de Geus,Franziska Degenhardt,Srdjan Djurovic,Gary Donohoe,Alysa E. Doyle,Jubao Duan,Frank Dudbridge,Eftichia Duketis,Richard P. Ebstein,Howard J. Edenberg,Josephine Elia,Sean Ennis,Bruno Etain,Ayman H. Fanous,Ayman H. Fanous,Anne Farmer,I. Nicol Ferrier,Matthew Flickinger,Eric Fombonne,Tatiana Foroud,Josef Frank,Barbara Franke,Christine Fraser,Robert Freedman,Nelson B. Freimer,Christine M. Freitag,Marion Friedl,Louise Frisén,Louise Gallagher,Pablo V. Gejman,Lyudmila Georgieva,Elliot S. Gershon,Daniel H. Geschwind,Ina Giegling,Michael Gill,Scott D. Gordon,Katherine Gordon-Smith,Katherine Gordon-Smith,Elaine K. Green,Tiffany A. Greenwood,Dorothy E. Grice,Magdalena Gross,Detelina Grozeva,Weihua Guan,Weihua Guan,Hugh Gurling,Lieuwe de Haan,Jonathan L. Haines,Hakon Hakonarson,Joachim Hallmayer,Steven P. Hamilton,Marian L. Hamshere,Thomas Hansen,Annette M. Hartmann,Martin Hautzinger,Andrew C. Heath,Anjali K. Henders,Stefan Herms,Stefan Herms,Ian B. Hickie,Maria Hipolito,Susanne Hoefels,Peter Holmans,Florian Holsboer,Witte J.G. Hoogendijk,Jouke-Jan Hottenga,Christina M. Hultman,Vanessa Hus,Andres Ingason,Marcus Ising,Stéphane Jamain,Edward G. Jones,Ian Jones,Lisa Jones,Jung-Ying Tzeng,Anna K. Kähler,René S. Kahn,Radhika Kandaswamy,Matthew C. Keller,James L. Kennedy,Elaine Kenny,Lindsey Kent,Yunjung Kim,George Kirov,Sabine M. Klauck,Lambertus Klei,James A. Knowles,Martin A. Kohli,Daniel L. Koller,Bettina Konte,Ania Korszun,Lydia Krabbendam,Robert Krasucki,Jonna Kuntsi,Phoenix Kwan,Mikael Landén,Mikael Landén,Niklas Långström,Mark Lathrop,Jacob Lawrence,William Lawson,Marion Leboyer,David H. Ledbetter,Phil Lee,Todd Lencz,Todd Lencz,Klaus-Peter Lesch,Klaus-Peter Lesch,Douglas F. Levinson,Cathryn M. Lewis,Jun Li,Paul Lichtenstein,Jeffrey A. Lieberman,Danyu Lin,Don H. Linszen,Chunyu Liu,Falk W. Lohoff,Sandra K. Loo,Catherine Lord,Jennifer K. Lowe,Susanne Lucae,Donald J. MacIntyre,Pamela A. F. Madden,Elena Maestrini,Patrik K. E. Magnusson,Pamela B. Mahon,Wolfgang Maier,Anil K. Malhotra,Anil K. Malhotra,Shrikant Mane,Christa Lese Martin,Nicholas G. Martin,Manuel Mattheisen,Manuel Mattheisen,Keith Matthews,Morten Mattingsdal,Steven A. McCarroll,Kevin A. McGhee,James J. McGough,Patrick J. McGrath,Peter McGuffin,Melvin G. McInnis,Andrew M. McIntosh,Rebecca McKinney,Alan W. McLean,Francis J. McMahon,William M. McMahon,Andrew McQuillin,Helena Medeiros,Sarah E. 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Potash,Fritz Poustka,Peter Propping,Vinay Puri,Digby Quested,Emma M. Quinn,Josep Antoni Ramos-Quiroga,Henrik B. Rasmussen,Soumya Raychaudhuri,Soumya Raychaudhuri,Karola Rehnström,Andreas Reif,Marta Ribasés,John P. Rice,Marcella Rietschel,Kathryn Roeder,Herbert Roeyers,Lizzy Rossin,Aribert Rothenberger,Guy A. Rouleau,Douglas M. Ruderfer,Dan Rujescu,Alan R. Sanders,Stephen Sanders,Susan L. Santangelo,Susan L. Santangelo,Joseph A. Sergeant,Russell Schachar,Martin Schalling,Alan F. Schatzberg,William A. Scheftner,Gerard D. Schellenberg,Stephen W. Scherer,Nicholas J. Schork,Thomas G. Schulze,Thomas G. Schulze,Johannes Schumacher,Markus J. Schwarz,Edward M. Scolnick,Laura J. Scott,Jianxin Shi,Paul D. Shilling,Stanley I. Shyn,Jeremy M. Silverman,Susan L. Slager,Susan L. Smalley,Johannes H. Smit,Erin N. Smith,Edmund J.S. Sonuga-Barke,Edmund J.S. Sonuga-Barke,David St Clair,Matthew W. 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Kendler,Naomi R. Wray +405 more
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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Clinical whole-exome sequencing for the diagnosis of mendelian disorders.
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TL;DR: W whole-exome sequencing identified the underlying genetic defect in 25% of consecutive patients referred for evaluation of a possible genetic condition.
Journal ArticleDOI
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
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TL;DR: The results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.
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Causes and consequences of replication stress.
TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
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