Altered splicing associated with the pathology of inflammatory bowel disease.
Altered splicing associated with the pathology of inflammatory bowel disease.
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DOI：
10.1186/s40246-021-00347-y
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发表时间：
2021-07-23
期刊：
影响因子：
4.5
通讯作者：
Gibson G
中科院分区：
文献类型：
--
作者：
Berger K;Somineni H;Prince J;Kugathasan S;Gibson G
个体基因的异常剪接是一种众所周知的促进多种疾病病理的机制，但疾病较少归因于外显子使用的全局破坏。为了探索异常剪接与炎症性肠病的可能关联，我们开发了一个量化转录丰度和外显子包含转录组的管道，并将其应用于回肠和直肠活检数据集，这些数据集来自34例儿童或年轻人溃疡性结肠炎和克罗恩病。表达和剪接在一定程度上是共同变化的，8个个体表现出异常的特征，这可以通过上皮细胞与基质细胞和免疫细胞的比例改变来解释。在选择性剪接中，还观察到与祖先相关的偏差占变异的5%，部分也与细胞类型比例有关。此外，还发现了两个人，他们有284个外显子，其中外显子的剪接率明显不同，包括已建立的IBD风险基因CEACAM1，这导致他们的回肠样本与直肠相似。这些结果表明，剪接使用的数量差异以一种以前未被认识到的方式促进了炎症性肠病的病理。在线版本包含补充材料，可在10.1186/s40246-021-00347-y获得。
Aberrant splicing of individual genes is a well-known mechanism promoting pathology for a wide range of conditions, but disease is less commonly attributed to global disruption of exon usage. To explore the possible association of aberrant splicing with inflammatory bowel disease, we developed a pipeline for quantifying transcript abundance and exon inclusion transcriptome-wide and applied it to a dataset of ileal and rectal biopsies, both obtained in duplicate from 34 pediatric or young adult cases of ulcerative colitis and Crohn’s disease. Expression and splicing covary to some extent, and eight individuals exhibited aberrant profiles that can be explained by altered ratios of epithelial to stromal and immune cells. Ancestry-related biases in alternative splicing accounting for 5% of the variance were also observed, in part also related to cell-type proportions. In addition, two individuals were identified who had 284 exons with significantly divergent percent spliced in exons, including in the established IBD risk gene CEACAM1, which caused their ileal samples to resemble the rectum. These results imply that quantitative differences in splice usage contribute to the pathology of inflammatory bowel disease in a previously unrecognized manner. The online version contains supplementary material available at 10.1186/s40246-021-00347-y.
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DOI：
10.1038/s41575-019-0118-x
发表时间：
2019-05
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Furey TS;Sethupathy P;Sheikh SZ
通讯作者：
Sheikh SZ
影响因子：
32.4
作者：
Chen L;Chen Z;Baker K;Halvorsen EM;da Cunha AP;Flak MB;Gerber G;Huang YH;Hosomi S;Arthur JC;Dery KJ;Nagaishi T;Beauchemin N;Holmes KV;Ho JW;Shively JE;Jobin C;Onderdonk AB;Bry L;Weiner HL;Higgins DE;Blumberg RS
通讯作者：
Blumberg RS
影响因子：
17.1
作者：
Cummings BB;Marshall JL;Tukiainen T;Lek M;Donkervoort S;Foley AR;Bolduc V;Waddell LB;Sandaradura SA;O'Grady GL;Estrella E;Reddy HM;Zhao F;Weisburd B;Karczewski KJ;O'Donnell-Luria AH;Birnbaum D;Sarkozy A;Hu Y;Gonorazky H;Claeys K;Joshi H;Bournazos A;Oates EC;Ghaoui R;Davis MR;Laing NG;Topf A;Genotype-Tissue Expression Consortium;Kang PB;Beggs AH;North KN;Straub V;Dowling JJ;Muntoni F;Clarke NF;Cooper ST;Bönnemann CG;MacArthur DG
通讯作者：
MacArthur DG
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.