title: Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements.
abstract: Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.|Applied Bioinformatics Laboratory, Atlanta, GA 30332, USA.|PanAmerican Bioinformatics Institute, Cali, Valle del Cauca, 760043, Colombia.|BIOS Centro de Bioinformática y Biología Computacional, Manizales, Caldas, 170002, Colombia.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Rishishwar
authors.affiliation: PanAmerican Bioinformatics Institute, Cali, Valle del Cauca, 760043, Colombia.|National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mariño-Ramírez
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.|Applied Bioinformatics Laboratory, Atlanta, GA 30332, USA.|PanAmerican Bioinformatics Institute, Cali, Valle del Cauca, 760043, Colombia.|BIOS Centro de Bioinformática y Biología Computacional, Manizales, Caldas, 170002, Colombia.
authors.forename: I King
authors.initials: IK
authors.lastname: Jordan
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D044383:Black People; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004251:DNA Transposable Elements / Q000276:immunology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D007113:Immunity, Innate; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D044465:White People
chemical_list: D016207:Cytokines; D004251:DNA Transposable Elements; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D011948:Receptors, Antigen, T-Cell