Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1742
Título: Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene
Autor: Sosnay, Patrick R.
Siklosi, Karen R.
Van Goor, Fredrick
Kaniecki, Kyle
Yu, Haihui
Sharma, Neeraj
Ramalho, Anabela S.
Amaral, Margarida D.
Dorfman, Ruslan
Zielenski, Julian
Masica, David L.
Karchin, Rachel
Millen, Linda
Thomas, Philip J.
Patrinos, George P.
Corey, Mary
Lewis, Michelle H.
Rommens, Johanna M.
Castellani, Carlo
Penland, Christopher M.
Cutting, Garry R.
Palavras-chave: Fibrose Quística
CFTR
Doenças Genéticas
Data: Out-2013
Editora: Nature Publishing Group
Citação: Nature Genetics, 2013, 45(10):1160-69; doi:10.1038/ng.2745
Resumo: Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation into clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator gene CFTR have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 individuals with cystic fibrosis in registries and clinics in North America and Europe. In these individuals, 159 CFTR variants had an allele frequency of ≥0.01%. These variants were evaluated for both clinical severity and functional consequence, with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of individuals with cystic fibrosis enabled assignment of 12 of the remaining 32 variants as neutral, whereas the other 20 variants remained of indeterminate effect. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically relevant genomic variation.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1742
ISSN: 1061-4036
Versão do Editor: http://www.nature.com/ng/journal/v45/n10/full/ng.2745.html
Aparece nas colecções:DGH - Artigos em revistas internacionais

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