RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE.
RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE.
复制标题
DOI：
10.1371/journal.pone.0054487
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Barnes BJ
中科院分区：
文献类型：
--
作者：
Stone RC;Du P;Feng D;Dhawan K;Rönnblom L;Eloranta ML;Donnelly R;Barnes BJ
Polymorphisms in the interferon regulatory factor 5 (IRF5) gene have been consistently replicated and shown to confer risk for or protection from the development of systemic lupus erythematosus (SLE). IRF5 expression is significantly upregulated in SLE patients and upregulation associates with IRF5-SLE risk haplotypes. IRF5 alternative splicing has also been shown to be elevated in SLE patients. Given that human IRF5 exists as multiple alternatively spliced transcripts with distinct function(s), it is important to determine whether the IRF5 transcript profile expressed in healthy donor immune cells is different from that expressed in SLE patients. Moreover, it is not currently known whether an IRF5-SLE risk haplotype defines the profile of IRF5 transcripts expressed. Using standard molecular cloning techniques, we identified and isolated 14 new differentially spliced IRF5 transcript variants from purified monocytes of healthy donors and SLE patients to generate an IRF5 variant transcriptome. Next-generation sequencing was then used to perform in-depth and quantitative analysis of full-length IRF5 transcript expression in primary immune cells of SLE patients and healthy donors by next-generation sequencing. Evidence for additional alternatively spliced transcripts was obtained from de novo junction discovery. Data from these studies support the overall complexity of IRF5 alternative splicing in SLE. Results from next-generation sequencing correlated with cloning and gave similar abundance rankings in SLE patients thus supporting the use of this new technology for in-depth single gene transcript profiling. Results from this study provide the first proof that 1) SLE patients express an IRF5 transcript signature that is distinct from healthy donors, 2) an IRF5-SLE risk haplotype defines the top four most abundant IRF5 transcripts expressed in SLE patients, and 3) an IRF5 transcript signature enables clustering of SLE patients with the H2 risk haplotype.
登录
查看更多内容
DOI：
10.1038/nrrheum.2010.176
发表时间：
2010-12
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Jarvinen, Tiina M.;Hellquist, Anna;Kere, Juha
通讯作者：
Kere, Juha
影响因子：
--
作者：
Kozyrev, Sergey V.;Lewen, Susanna;Alarcon-Riquelme, Marta E.
通讯作者：
Alarcon-Riquelme, Marta E.
影响因子：
3.5
作者：
Kozyrev, Sergey V.;Alarcon-Riquelme, Marta E.
通讯作者：
Alarcon-Riquelme, Marta E.
影响因子：
4.4
作者：
Flesher DL;Sun X;Behrens TW;Graham RR;Criswell LA
通讯作者：
Criswell LA