Abstract:
:Type-1 reactions (T1R) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the genewise enrichment of rare protein-altering variants in 7 genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy patients of which 237 were T1R-affected and 237 were T1R-free matched controls. Genewise enrichment of nonsynonymous variants was tested with both kernel-based (sequence kernel association test [SKAT]) and burden methods. Of the 7 genes tested 2 showed statistical evidence of association with T1R. For the LRRK2 gene an enrichment of nonsynonymous variants was observed in T1R-free controls (PSKAT-O = 1.6 × 10-4). This genewise association was driven almost entirely by the gain-of-function variant R1628P (P = 0.004; odds ratio = 0.29). The second genewise association was found for the Parkin coding gene PRKN (formerly PARK2) where 7 rare variants were enriched in T1R-affected cases (PSKAT-O = 7.4 × 10-5). Mutations in both PRKN and LRRK2 are known causes of Parkinson's disease (PD). Hence, we evaluated to what extent such rare amino acid changes observed in T1R are shared with PD. We observed that amino acids in Parkin targeted by nonsynonymous T1R-risk mutations were also enriched for mutations implicated in PD (P = 1.5 × 10-4). Hence, neuroinflammation in PD and peripheral nerve damage due to inflammation in T1R share overlapping genetic control of pathogenicity.
journal_name
Proc Natl Acad Sci U S Aauthors
Fava VM,Xu YZ,Lettre G,Van Thuc N,Orlova M,Thai VH,Tao S,Croteau N,Eldeeb MA,MacDougall EJ,Cambri G,Lahiri R,Adams L,Fon EA,Trempe JF,Cobat A,Alcaïs A,Abel L,Schurr Edoi
10.1073/pnas.1901805116subject
Has Abstractpub_date
2019-07-30 00:00:00pages
15616-15624issue
31eissn
0027-8424issn
1091-6490pii
1901805116journal_volume
116pub_type
临床试验,杂志文章,多中心研究abstract::Pneumococcal peptidoglycan amidase (N-acetylmuramoyl-L-alanine amidase, EC 3.5.1.28) and phage CPL1 lysozyme degrade a common substrate (choline-containing pneumococcal cell walls); the former hydrolyzes the bond between muramic acid and alanine, whereas the latter breaks down the linkage between muramic acid and gluc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.20.8125
更新日期:1990-10-01 00:00:00
abstract::We have examined the effect of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and cycloheximide on the CV-1 cell cytoskeleton. Within a few hours after producing an inhibition of cellular protein synthesis, all these agents specifically disrupted the organization of the vimentin filament system with no discernab...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.12.7267
更新日期:1980-12-01 00:00:00
abstract::IscR (iron-sulfur cluster regulator) is encoded by an ORF located immediately upstream of genes coding for the Escherichia coli Fe-S cluster assembly proteins, IscS, IscU, and IscA. IscR shares amino acid similarity with MarA, a member of the MarA/SoxS/Rob family of transcription factors. In this study, we found that ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.251550898
更新日期:2001-12-18 00:00:00
abstract::All but two genes involved in the ergosterol biosynthetic pathway in Saccharomyces cerevisiae have been cloned, and their corresponding mutants have been described. The remaining genes encode the C-3 sterol dehydrogenase (C-4 decarboxylase) and the 3-keto sterol reductase and in concert with the C-4 sterol methyloxida...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.23.13794
更新日期:1998-11-10 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1108790109
更新日期:2012-02-21 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:1976-02-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.8.3033
更新日期:1991-04-15 00:00:00
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更新日期:1997-03-04 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1998-09-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1111043108
更新日期:2011-12-13 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.11.5515
更新日期:1979-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0912896107
更新日期:2010-09-28 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章,评审
doi:10.1073/pnas.93.21.11421
更新日期:1996-10-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1815682116
更新日期:2019-03-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1311029111
更新日期:2014-03-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.20.9302
更新日期:1994-09-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2016-04-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.9.4493
更新日期:2000-04-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.8.2770
更新日期:1976-08-01 00:00:00
abstract::Transcription factor TFIID consists of TATA binding protein (TBP) and at least eight TBP-associated factors (TAFs). As TAFs are required for activated but not basal transcription, we have proposed that TAFs act as coactivators to mediate signals between activators and the basal transcription machinery. Here we report ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.13.5788
更新日期:1995-06-20 00:00:00
abstract::The rpoN gene encoding the transcription factor sigma54 in Myxococcus xanthus has been cloned using a heterologous rpoN probe. The sequence of the cross-hybridizing DNA confirmed the existence of an ORF 1518 bp long that encodes a well conserved member of the sigma54 family of sigma factors. Low- as well as high-strin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.5.1979
更新日期:1997-03-04 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1319681110
更新日期:2013-12-10 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0403959101
更新日期:2004-10-12 00:00:00