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Guidelines for investigating causality of sequence variants in human disease

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive report...

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Autores principales: MacArthur, D. G., Manolio, T. A., Dimmock, D. P., Rehm, H. L., Shendure, J., Abecasis, G. R., Adams, D. R., Altman, R. B., Antonarakis, S. E., Ashley, E. A., Barrett, J. C., Biesecker, L. G., Conrad, D. F., Cooper, G. M., Cox, N. J., Daly, M. J., Gerstein, M. B., Goldstein, D. B., Hirschhorn, J. N., Leal, S. M., Pennacchio, L. A., Stamatoyannopoulos, J. A., Sunyaev, S. R., Valle, D., Voight, B. F., Winckler, W., Gunter, C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180223/
https://www.ncbi.nlm.nih.gov/pubmed/24759409
http://dx.doi.org/10.1038/nature13127
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author MacArthur, D. G.
Manolio, T. A.
Dimmock, D. P.
Rehm, H. L.
Shendure, J.
Abecasis, G. R.
Adams, D. R.
Altman, R. B.
Antonarakis, S. E.
Ashley, E. A.
Barrett, J. C.
Biesecker, L. G.
Conrad, D. F.
Cooper, G. M.
Cox, N. J.
Daly, M. J.
Gerstein, M. B.
Goldstein, D. B.
Hirschhorn, J. N.
Leal, S. M.
Pennacchio, L. A.
Stamatoyannopoulos, J. A.
Sunyaev, S. R.
Valle, D.
Voight, B. F.
Winckler, W.
Gunter, C.
author_facet MacArthur, D. G.
Manolio, T. A.
Dimmock, D. P.
Rehm, H. L.
Shendure, J.
Abecasis, G. R.
Adams, D. R.
Altman, R. B.
Antonarakis, S. E.
Ashley, E. A.
Barrett, J. C.
Biesecker, L. G.
Conrad, D. F.
Cooper, G. M.
Cox, N. J.
Daly, M. J.
Gerstein, M. B.
Goldstein, D. B.
Hirschhorn, J. N.
Leal, S. M.
Pennacchio, L. A.
Stamatoyannopoulos, J. A.
Sunyaev, S. R.
Valle, D.
Voight, B. F.
Winckler, W.
Gunter, C.
author_sort MacArthur, D. G.
collection PubMed
description The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.
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spelling pubmed-41802232014-10-24 Guidelines for investigating causality of sequence variants in human disease MacArthur, D. G. Manolio, T. A. Dimmock, D. P. Rehm, H. L. Shendure, J. Abecasis, G. R. Adams, D. R. Altman, R. B. Antonarakis, S. E. Ashley, E. A. Barrett, J. C. Biesecker, L. G. Conrad, D. F. Cooper, G. M. Cox, N. J. Daly, M. J. Gerstein, M. B. Goldstein, D. B. Hirschhorn, J. N. Leal, S. M. Pennacchio, L. A. Stamatoyannopoulos, J. A. Sunyaev, S. R. Valle, D. Voight, B. F. Winckler, W. Gunter, C. Nature Article The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. 2014-04-24 /pmc/articles/PMC4180223/ /pubmed/24759409 http://dx.doi.org/10.1038/nature13127 Text en This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
spellingShingle Article
MacArthur, D. G.
Manolio, T. A.
Dimmock, D. P.
Rehm, H. L.
Shendure, J.
Abecasis, G. R.
Adams, D. R.
Altman, R. B.
Antonarakis, S. E.
Ashley, E. A.
Barrett, J. C.
Biesecker, L. G.
Conrad, D. F.
Cooper, G. M.
Cox, N. J.
Daly, M. J.
Gerstein, M. B.
Goldstein, D. B.
Hirschhorn, J. N.
Leal, S. M.
Pennacchio, L. A.
Stamatoyannopoulos, J. A.
Sunyaev, S. R.
Valle, D.
Voight, B. F.
Winckler, W.
Gunter, C.
Guidelines for investigating causality of sequence variants in human disease
title Guidelines for investigating causality of sequence variants in human disease
title_full Guidelines for investigating causality of sequence variants in human disease
title_fullStr Guidelines for investigating causality of sequence variants in human disease
title_full_unstemmed Guidelines for investigating causality of sequence variants in human disease
title_short Guidelines for investigating causality of sequence variants in human disease
title_sort guidelines for investigating causality of sequence variants in human disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180223/
https://www.ncbi.nlm.nih.gov/pubmed/24759409
http://dx.doi.org/10.1038/nature13127
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