Discovering Single Nucleotide Polymorphisms Regulating Human Gene Expression Using Allele Specific Expression from RNA-seq Data. 2016

Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
Department of Computer Science, University of California, Los Angeles, California 90095-1596.

The study of the genetics of gene expression is of considerable importance to understanding the nature of common, complex diseases. The most widely applied approach to identifying relationships between genetic variation and gene expression is the expression quantitative trait loci (eQTL) approach. Here, we increased the computational power of eQTL with an alternative and complementary approach based on analyzing allele specific expression (ASE). We designed a novel analytical method to identify cis-acting regulatory variants based on genome sequencing and measurements of ASE from RNA-sequencing (RNA-seq) data. We evaluated the power and resolution of our method using simulated data. We then applied the method to map regulatory variants affecting gene expression in lymphoblastoid cell lines (LCLs) from 77 unrelated northern and western European individuals (CEU), which were part of the HapMap project. A total of 2309 SNPs were identified as being associated with ASE patterns. The SNPs associated with ASE were enriched within promoter regions and were significantly more likely to signal strong evidence for a regulatory role. Finally, among the candidate regulatory SNPs, we identified 108 SNPs that were previously associated with human immune diseases. With further improvements in quantifying ASE from RNA-seq, the application of our method to other datasets is expected to accelerate our understanding of the biological basis of common diseases.

UI MeSH Term Description Entries
D007154 Immune System Diseases Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both. Immune Disorders,Immune System Disorders,Immunologic Diseases,Diseases of Immune System,Immune Diseases,Immunological Diseases,Disease, Immune,Disease, Immune System,Disease, Immunologic,Disease, Immunological,Disorder, Immune System,Immune Disease,Immune Disorder,Immune System Disease,Immune System Disorder,Immunologic Disease,Immunological Disease
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D005060 Europe The continent north of AFRICA, west of ASIA and east of the ATLANTIC OCEAN. Northern Europe,Southern Europe,Western Europe
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D044465 White People Persons having origins in any of the white racial groups of Europe, the Middle East, or North Africa. Note that OMB category WHITE is available for the United States population groups. Race and ethnicity terms, as used in the federal government, are self-identified social construct and may include terms outdated and offensive in MeSH to assist users who are interested in retrieving comprehensive search results for studies such as in longitudinal studies. European Continental Ancestry Group,White Person,Caucasian Race,Caucasoid Race,Caucasian Races,Caucasoid Races,People, White,Person, White,Race, Caucasian,Race, Caucasoid,White Peoples,White Persons
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D055106 Genome-Wide Association Study An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers to identify gene candidates or quantitative trait loci associated with a specific organism trait or specific disease or condition. Genome Wide Association Analysis,Genome Wide Association Study,GWA Study,Genome Wide Association Scan,Genome Wide Association Studies,Whole Genome Association Analysis,Whole Genome Association Study,Association Studies, Genome-Wide,Association Study, Genome-Wide,GWA Studies,Genome-Wide Association Studies,Studies, GWA,Studies, Genome-Wide Association,Study, GWA,Study, Genome-Wide Association
D059467 Transcriptome The pattern of GENE EXPRESSION at the level of genetic transcription in a specific organism or under specific circumstances in specific cells. Transcriptomes,Gene Expression Profiles,Gene Expression Signatures,Transcriptome Profiles,Expression Profile, Gene,Expression Profiles, Gene,Expression Signature, Gene,Expression Signatures, Gene,Gene Expression Profile,Gene Expression Signature,Profile, Gene Expression,Profile, Transcriptome,Profiles, Gene Expression,Profiles, Transcriptome,Signature, Gene Expression,Signatures, Gene Expression,Transcriptome Profile

Related Publications

Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
January 2014, Methods in molecular biology (Clifton, N.J.),
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
August 2015, Bioinformatics (Oxford, England),
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
November 2014, Genes to cells : devoted to molecular & cellular mechanisms,
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
June 2020, Bioinformatics (Oxford, England),
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
January 2024, Biometrics,
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
January 2015, PloS one,
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
October 2011, Genome research,
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
December 2017, Genome biology,
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
September 2014, Bioinformatics (Oxford, England),
Eun Yong Kang, and Lisa J Martin, and Serghei Mangul, and Warin Isvilanonda, and Jennifer Zou, and Eyal Ben-David, and Buhm Han, and Aldons J Lusis, and Sagiv Shifman, and Eleazar Eskin
January 2011, Cancer informatics,
Copied contents to your clipboard!