Vex-seq: high-throughput identification of the impact of genetic variation on pre-mRNA splicing efficiency

被引：60

作者：

Adamson, Scott I. ^{[1
]}

Zhan, Lijun ^{[1
]}

Graveley, Brenton R. ^{[1
]}

机构：

[1] UConn Hlth, Inst Syst Genom, Dept Genet & Genome Sci, Farmington, CT 06030 USA

来源：

GENOME BIOLOGY | 2018年 / 19卷

关键词：

SEQUENCE MOTIFS; BRANCHPOINTS; NONSENSE; ELEMENTS; DISEASE; CONTEXT; CODE;

D O I：

10.1186/s13059-018-1437-x

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Understanding the functional impact of genomic variants is a major goal of modern genetics and personalized medicine. Although many synonymous and non-coding variants act through altering the efficiency of pre-mRNA splicing, it is difficult to predict how these variants impact pre-mRNA splicing. Here, we describe a massively parallel approach we use to test the impact on pre-mRNA splicing of 2059 human genetic variants spanning 110 alternative exons. This method, called variant exon sequencing (Vex-seq), yields data that reinforce known mechanisms of pre-mRNA splicing, identifies variants that impact pre-mRNA splicing, and will be useful for increasing our understanding of genome function.

引用

页数：12

共 31 条

[21] Learning the Sequence Determinants of Alternative Splicing from Millions of Random Sequences [J].

Rosenberg, Alexander B. ;

Patwardhan, Rupali P. ;

Shendure, Jay ;

Seelig, Georg .

CELL, 2015, 163 (03) :698-711

[22] RNA mis-splicing in disease [J].

Scotti, Marina M. ;

Swanson, Maurice S. .

NATURE REVIEWS GENETICS, 2016, 17 (01) :19-32

[23] rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data [J].

Shen, Shihao ;

Park, Juw Won ;

Lu, Zhi-xiang ;

Lin, Lan ;

Henry, Michael D. ;

Wu, Ying Nian ;

Zhou, Qing ;

Xing, Yi .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (51) :E5593-E5601

[24] Machine learning annotation of human branchpoints [J].

Signal, Bethany ;

Gloss, Brian S. ;

Dinger, Marcel E. ;

Mercer, Tim R. .

BIOINFORMATICS, 2018, 34 (06) :920-927

[25] The effects of structure on pre-mRNA processing and stability [J].

Soemedi, Rachel ;

Cygan, Kamil J. ;

Rhine, Christy L. ;

Glidden, David T. ;

Taggart, Allison J. ;

Lin, Chien-Ling ;

Fredericks, Alger M. ;

Fairbrother, William G. .

METHODS, 2017, 125 :36-44

[26] Pathogenic variants that alter protein code often disrupt splicing [J].

Soemedi, Rachel ;

Cygan, Kamil J. ;

Rhine, Christy L. ;

Wang, Jing ;

Bulacan, Charlston ;

Yang, John ;

Bayrak-Toydemir, Pinar ;

McDonald, Jamie ;

Fairbrother, William G. .

NATURE GENETICS, 2017, 49 (06) :848-+

[27] Does conservation account for splicing patterns? [J].

Wainberg, Michael ;

Alipanahi, Babak ;

Frey, Brendan .

BMC GENOMICS, 2016, 17

[28] Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules [J].

Wang, Yang ;

Ma, Meng ;

Xiao, Xinshu ;

Wang, Zefeng .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (10) :1044-U104

[29] The human splicing code reveals new insights into the genetic determinants of disease [J].

Xiong, Hui Y. ;

Alipanahi, Babak ;

Lee, Leo J. ;

Bretschneider, Hannes ;

Merico, Daniele ;

Yuen, Ryan K. C. ;

Hua, Yimin ;

Gueroussov, Serge ;

Najafabadi, Hamed S. ;

Hughes, Timothy R. ;

Morris, Quaid ;

Barash, Yoseph ;

Krainer, Adrian R. ;

Jojic, Nebojsa ;

Scherer, Stephen W. ;

Blencowe, Benjamin J. ;

Frey, Brendan J. .

SCIENCE, 2015, 347 (6218)

[30] Bayesian prediction of tissue-regulated splicing using RNA sequence and cellular context [J].

Xiong, Hui Yuan ;

Barash, Yoseph ;

Frey, Brendan J. .

BIOINFORMATICS, 2011, 27 (18) :2554-2562

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