title: Populational landscape of INDELs affecting transcription factor-binding sites in humans.
abstract: BACKGROUND
  Differences in gene expression have a significant role in the diversity of phenotypes in humans. Here we integrated human public data from ENCODE, 1000 Genomes and Geuvadis to explore the populational landscape of INDELs affecting transcription factor-binding sites (TFBS). A significant fraction of TFBS close to the transcription start site of known genes is affected by INDELs with a consequent effect at the expression of the associated gene.
  
  
  RESULTS
  Hundreds of TFBS-affecting INDELs (TFBS-ID) show a differential frequency between human populations, suggesting a role of natural selection in the spread of such variant INDELs. A comparison with a dataset of known human genomic regions under natural selection allowed us to identify several cases of TFBS-ID likely involved in populational adaptations. Ontology analyses on the differential TFBS-ID further indicated several biological processes under natural selection in different populations.
  
  
  CONCLUSIONS
  Together, our results strongly suggest that INDELs have an important role in modulating gene expression patterns in humans. The dataset we make available, together with other data reporting variability at both regulatory and coding regions of genes, represent a powerful tool for studies aiming to better understand the evolution of gene regulatory networks in humans.
authors.affiliation: PhD Program in Genetics and Molecular Biology, UFPA, Belém, PA, Brazil. andremrsantos@gmail.com.
authors.forename: André M
authors.initials: AM
authors.lastname: Ribeiro-dos-Santos
authors.affiliation: PhD Program in Genetics and Molecular Biology, UFPA, Belém, PA, Brazil. clecio.de@gmail.com.|Instituto de Bioinformática e Biotecnologia, Natal, RN, Brazil. clecio.de@gmail.com.
authors.forename: Vandeclécio L
authors.initials: VL
authors.lastname: da Silva
authors.affiliation: Instituto de Bioinformática e Biotecnologia, Natal, RN, Brazil. Jorge@i2bio.org.|Instituto Metrópole Digital, UFRN, Natal, RN, Brazil. Jorge@i2bio.org.
authors.forename: Jorge E S
authors.initials: JE
authors.lastname: de Souza
authors.affiliation: Brain Institute, UFRN, Av. Nascimento de Castro, 2155 - 59056-450, Natal, RN, Brazil. sandro@neuro.ufrn.br.
authors.forename: Sandro J
authors.initials: SJ
authors.lastname: de Souza
mesh_terms: D001665:Binding Sites / Q000235:genetics*; D002874:Chromosome Mapping; D015894:Genome, Human; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics*; D024363:Transcription Initiation Site
chemical_list: D014157:Transcription Factors