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

[1]

Adamson SI, VEX SEQ V1 0, DOI [10.5281/zenodo.1217642, DOI 10.5281/ZENODO.1217642]

[2]

[Anonymous], VEX SEQ HIGH THROUGH

[3] Listening to silence and understanding nonsense: Exonic mutations that affect splicing [J].

Cartegni, L ;

Chew, SL ;

Krainer, AR .

NATURE REVIEWS GENETICS, 2002, 3 (04) :285-298

[4]

Cheung R, 2018, BIORXIV

[5] Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors [J].

Culler, Stephanie J. ;

Hoff, Kevin G. ;

Voelker, Rodger B. ;

Berglund, J. Andrew ;

Smolke, Christina D. .

NUCLEIC ACIDS RESEARCH, 2010, 38 (15) :5152-5165

[6] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[7] Alternative splicing in disease and therapy [J].

Garcia-Blanco, MA ;

Baraniak, AP ;

Lasda, EL .

NATURE BIOTECHNOLOGY, 2004, 22 (05) :535-546

[8] STABILIZATION AND RIBOSOME ASSOCIATION OF UNSPLICED PREMESSENGER RNAS IN A YEAST UPFL- MUTANT [J].

HE, F ;

PELTZ, SW ;

DONAHUE, JL ;

ROSBASH, M ;

JACOBSON, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) :7034-7038

[9] Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening [J].

Joung, Julia ;

Konermann, Silvana ;

Gootenberg, Jonathan S. ;

Abudayyeh, Omar O. ;

Platt, Randall J. ;

Brigham, Mark D. ;

Sanjana, Neville E. ;

Zhang, Feng .

NATURE PROTOCOLS, 2017, 12 (04) :828-863

[10] Quantitative evaluation of all hexamers as exonic splicing elements [J].

Ke, Shengdong ;

Shang, Shulian ;

Kalachikov, Sergey M. ;

Morozova, Irina ;

Yu, Lin ;

Russo, James J. ;

Ju, Jingyue ;

Chasin, Lawrence A. .

GENOME RESEARCH, 2011, 21 (08) :1360-1374

← 1 2 3 4 →