Journal ArticleDOI
Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis
Simon G. Gregory,Silke Schmidt,Puneet Seth,Jorge R. Oksenberg,John Hart,Angela Prokop,Stacy J. Caillier,Maria Ban,An Goris,Lisa F. Barcellos,Robin R. Lincoln,Jacob L. McCauley,Stephen Sawcer,D. A. S. Compston,Bénédicte Dubois,Stephen L. Hauser,Mariano A. Garcia-Blanco,Margaret A. Pericak-Vance,Jonathan L. Haines +18 more
TLDR
Allelic association of a polymorphism in the gene encoding the interleukin 7 receptor α chain ( IL7R) is described as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets.Abstract:
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor α chain ( IL7R ) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 × 10−7). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.read more
Citations
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Risk alleles for multiple sclerosis identified by a genomewide study.
David A. Hafler,Alastair Compston,Stephen Sawcer,Mark J. Daly,Philip L. De Jager,Stacey Gabriel,Daniel B. Mirel,Adrian J. Ivinson,Margaret A. Pericak-Vance,Simon G. Gregory,John D. Rioux,John D. Rioux,Jacob L. McCauley,Lisa F. Barcellos,Lisa F. Barcellos,Bruce A.C. Cree,Stephen L. Hauser +16 more
TL;DR: Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis.
Journal ArticleDOI
Multiple Sclerosis: An Immune or Neurodegenerative Disorder?
Bruce D. Trapp,Klaus-Armin Nave +1 more
TL;DR: Data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients are reviewed and it is questioned whether inflammatory demyelination is primary or secondary in the disease process.
Journal ArticleDOI
Immunopathology of multiple sclerosis
TL;DR: The current understanding of multiple sclerosis immunopathology is discussed, long-standing hypotheses regarding the role of the immune system in the disease are evaluated, and key questions that are still unanswered are delineated.
Journal ArticleDOI
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
Carl A. Anderson,Gabrielle Boucher,Charlie W. Lees,Andre Franke,Mauro D'Amato,Kent D. Taylor,James Lee,Philippe Goyette,Marcin Imielinski,Anna Latiano,Caroline Lagacé,Regan Scott,Leila Amininejad,Suzannah Bumpstead,Leonard Baidoo,Robert N. Baldassano,Murray L. Barclay,Theodore M. Bayless,Stephan Brand,Carsten Büning,Jean-Frederic Colombel,Lee A. Denson,Martine De Vos,Marla Dubinsky,Cathryn Edwards,David Ellinghaus,Rudolf S N Fehrmann,James A B Floyd,Timothy H. Florin,Denis Franchimont,Lude Franke,Michel Georges,Jürgen Glas,Nicole L. Glazer,Stephen L. Guthery,Talin Haritunians,Nicholas K. Hayward,Jean-Pierre Hugot,Gilles Jobin,Debby Laukens,Ian C. Lawrance,Marc Lémann,Arie Levine,Cécile Libioulle,Edouard Louis,Dermot P.B. McGovern,Monica Milla,Grant W. Montgomery,Katherine I. Morley,Craig Mowat,Aylwin Ng,William G. Newman,Roel A. Ophoff,Laura Papi,Orazio Palmieri,Laurent Peyrin-Biroulet,Julián Panés,Anne M. Phillips,Natalie J. Prescott,Deborah D. Proctor,Rebecca L. Roberts,Richard K Russell,Paul Rutgeerts,Jeremy D. Sanderson,Miquel Sans,Philip Schumm,Frank Seibold,Yashoda Sharma,Lisa A. Simms,Mark Seielstad,Mark Seielstad,A. Hillary Steinhart,Stephan R. Targan,Leonard H. van den Berg,Morten H. Vatn,Hein W. Verspaget,Thomas D. Walters,Cisca Wijmenga,David C. Wilson,Harm-Jan Westra,Ramnik J. Xavier,Zhen Zhen Zhao,Cyriel Y. Ponsioen,Vibeke Andersen,Leif Törkvist,Maria Gazouli,Nicholas P. Anagnou,Tom H. Karlsen,Limas Kupčinskas,Jurgita Sventoraityte,John C. Mansfield,Subra Kugathasan,Mark S. Silverberg,Jonas Halfvarson,Jerome I. Rotter,Christopher G. Mathew,Anne M. Griffiths,Richard B. Gearry,Tariq Ahmad,Steven R. Brant,Mathias Chamaillard,Jack Satsangi,Judy H. Cho,Stefan Schreiber,Mark J. Daly,Jeffrey C. Barrett,Miles Parkes,Vito Annese,Hakon Hakonarson,Graham L. Radford-Smith,Richard H. Duerr,Severine Vermeire,Rinse K. Weersma,John D. Rioux +113 more
TL;DR: A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.
Journal ArticleDOI
Induction and molecular signature of pathogenic TH17 cells
Youjin Lee,Amit Awasthi,Amit Awasthi,Nir Yosef,Nir Yosef,Francisco J. Quintana,Sheng Xiao,Anneli Peters,Chuan Wu,Markus Kleinewietfeld,Sharon R. Kunder,David A. Hafler,Raymond A. Sobel,Aviv Regev,Aviv Regev,Vijay K. Kuchroo +15 more
TL;DR: It is found that the production of TGF-β3 by developing Th17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells, which had a molecular signature that defined pathogenic effector TH 17 cells in autoimmune disease.
References
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
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Complement factor H variant increases the risk of age-related macular degeneration.
Jonathan L. Haines,Michael A. Hauser,Silke Schmidt,William K. Scott,Lana M. Olson,Paul Gallins,Kylee L. Spencer,Shu Ying Kwan,Maher A. Noureddine,John R. Gilbert,Nathalie Schnetz-Boutaud,Anita Agarwal,Eric A. Postel,Margaret A. Pericak-Vance +13 more
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Journal ArticleDOI
Identification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
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TL;DR: Four error-checking algorithms are implemented in a new computer program, PedCheck, which will assist researchers in identifying all Mendelian inconsistencies in pedigree data and will provide them with useful and detailed diagnostic information to help resolve the errors.
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