Recent developments in genetic/genomic medicine.
Rachel Horton,Anneke Lucassen +1 more
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TLDR
The ways in which genetic medicine is developing in light of technological advances are outlined, including the landscape of treatment options for genetic conditions is shifting, which has evolving implications for clinical discussions around previously untreatable disorders.Abstract:
Advances in genetic technology are having a major impact in the clinic, and mean that many perceptions of the role and scope of genetic testing are having to change. Genomic testing brings with it a greater opportunity for diagnosis, or predictions of future diagnoses, but also an increased chance of uncertain or unexpected findings, many of which may have impacts for multiple members of a person’s family. In the past, genetic testing was rarely able to provide rapid results, but the increasing speed and availability of genomic testing is changing this, meaning that genomic information is increasingly influencing decisions around patient care in the acute inpatient setting. The landscape of treatment options for genetic conditions is shifting, which has evolving implications for clinical discussions around previously untreatable disorders. Furthermore, the point of access to testing is changing with increasing provision direct to the consumer outside the formal healthcare setting. This review outlines the ways in which genetic medicine is developing in light of technological advances.read more
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Journal ArticleDOI
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature
Margot R.F. Reijnders,Robert Janowski,Mohsan Alvi,Jay E. Self,Jay E. Self,Ton van Essen,Maaike Vreeburg,Rob P.W. Rouhl,Servi J. C. Stevens,Alexander P.A. Stegmann,Jolanda H. Schieving,Rolph Pfundt,Katinke Van Dijk,Eric Smeets,Connie T.R.M. Stumpel,Levinus A. Bok,Jan Maarten Cobben,Marc Engelen,Sahar Mansour,Margo Whiteford,Kate Chandler,Sofia Douzgou,Nicola S. Cooper,Ene-Choo Tan,Roger Foo,Roger Foo,Roger Foo,Angeline H. M. Lai,Julia Rankin,Andrew Green,Tuula Lönnqvist,Pirjo Isohanni,Shelley Williams,Ilene S. Ruhoy,Karen S. Carvalho,James J. Dowling,Dorit Lev,Katalin Sterbova,Petra Laššuthová,Jana Neupauerová,Jeff L. Waugh,Sotirios Keros,Jill Clayton-Smith,Sarah F. Smithson,Han G. Brunner,Han G. Brunner,Ceciel Van Hoeckel,Mel Anderson,Virginia Clowes,Victoria Mok Siu,Paulo Selber,Richard J. Leventer,Christoffer Nellåker,Dierk Niessing,David Hunt,David Hunt,Diana Baralle,Diana Baralle,Diana Baralle +58 more
TL;DR: The clinical spectrum of PURA syndrome is delineated with the identification of 32 additional individuals and genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity, which points towards the clinical recognisability of the syndrome.
Journal ArticleDOI
Unlocking the efficiency of genomics laboratories with robotic liquid-handling
TL;DR: The state-of-the-art technology of both sophisticated and do-it-yourself (DIY) robotic liquid-handlers are described and a practical review of the motivation, implications and requirements of laboratory automation for genome sequencing experiments is provided.
Journal ArticleDOI
Understanding genomics and the immune environment of penile cancer to improve therapy
Ahmet M. Aydin,Jad Chahoud,Jacob J. Adashek,Mounsif Azizi,Anthony M. Magliocco,Jeffrey S. Ross,Jeffrey S. Ross,Andrea Necchi,Philippe E. Spiess +8 more
TL;DR: Penile squamous cell carcinoma (PSCC) displays a wide range of therapeutically targetable somatic alterations, and patients with treatment-resistant advanced PSCC might benefit from combined and sequential targeted therapies.
Journal ArticleDOI
Next Generation Sequencing and Bioinformatics Analysis of Family Genetic Inheritance.
Aquillah M. Kanzi,James Emmanuel San,Benjamin Chimukangara,Eduan Wilkinson,Maryam Fish,Veron Ramsuran,Tulio de Oliveira +6 more
TL;DR: Next generation and third generation sequencing platforms, bioinformatic tools and genetic resources commonly used to analyze family based genomic data with a focus on identifying inherited or novel disease-causing mutations are discussed.
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Grant,Carla Gallo,Giovanni Poletti,Danish Saleheen,Asif Rasheed,Lisa D. Brooks,Adam Felsenfeld,Jean E. McEwen,Yekaterina Vaydylevich,Audrey Duncanson,Michael Dunn,Jeffery A. Schloss +517 more
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Journal ArticleDOI
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development.
Journal ArticleDOI
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing
Robert C. Green,Robert C. Green,Jonathan S. Berg,Wayne W. Grody,Sarah S. Kalia,Bruce R. Korf,Christa Lese Martin,Amy L. McGuire,Robert L. Nussbaum,Julianne M. O’Daniel,Kelly E. Ormond,Heidi L. Rehm,Heidi L. Rehm,Michael S. Watson,Marc S. Williams,Leslie G. Biesecker +15 more
TL;DR: It is recommended that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here and encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.
Journal ArticleDOI
Mutational Processes Molding the Genomes of 21 Breast Cancers
Serena Nik-Zainal,Ludmil B. Alexandrov,David C. Wedge,Peter Van Loo,Peter Van Loo,Peter Van Loo,Christopher Greenman,Christopher Greenman,Christopher Greenman,Keiran Raine,David T. Jones,Jonathan Hinton,John D Marshall,Lucy Stebbings,Andrew Menzies,Sancha Martin,Kenric Leung,Lina Chen,Catherine Leroy,Manasa Ramakrishna,Richard Rance,King Wai Lau,Laura Mudie,Ignacio Varela,David J. McBride,Graham R. Bignell,Susanna L. Cooke,Adam Shlien,John Gamble,Ian Whitmore,Mark Maddison,Patrick S. Tarpey,Helen Davies,Elli Papaemmanuil,Philip J. Stephens,Stuart McLaren,Adam Butler,Jon W. Teague,Göran Jönsson,Judy Garber,Daniel P. Silver,Penelope Miron,Aquila Fatima,Sandrine Boyault,Anita Langerød,Andrew Tutt,John W.M. Martens,Samuel Aparicio,Åke Borg,Anne Vincent Salomon,Gilles Thomas,Anne Lise Børresen-Dale,Anne Lise Børresen-Dale,Andrea L. Richardson,Michael S. Neuberger,P. Andrew Futreal,Peter J. Campbell,Peter J. Campbell,Peter J. Campbell,Michael R. Stratton +59 more
TL;DR: This work generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes, finding a remarkable phenomenon of localized hypermutation, termed “kataegis,” was observed.