title: Exome-based Variant Detection in Core Promoters.
abstract: Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data from three cell types of CD4+ T cells, CD19+ B cells and neutrophils of a single individual, we characterized the features of core promoter-mapped exome sequences, and analysed core-promoter variation in this individual genome. We also compared the core promoters between YRI (Yoruba in Ibadan, Nigeria) and the CEU (Utah residents of European decedent) populations using the exome data generated by the 1000 Genome project, and observed much higher variation in YRI population than in CEU population. Our study demonstrates that the EVDC method provides a simple but powerful means for genome-wile de novo characterization of core promoter sequence variation.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, Omaha, NE 68198, USA.
authors.forename: Yeong C
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, Omaha, NE 68198, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, Omaha, NE 68198, USA.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, Omaha, NE 68198, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Downs
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, Omaha, NE 68198, USA.
authors.forename: San Ming
authors.initials: SM
authors.lastname: Wang
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D059472:Exome; D014644:Genetic Variation; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D009504:Neutrophils / Q000378:metabolism; D009549:Nigeria; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014589:Utah