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Identification of bovine CpG SNPs as potential targets for epigenetic regulation via DNA methylation


Autoři: Mariângela B. C. Maldonado aff001;  Nelson B. de Rezende Neto aff002;  Sheila T. Nagamatsu aff003;  Marcelo F. Carazzolle aff003;  Jesse L. Hoff aff006;  Lynsey K. Whitacre aff006;  Robert D. Schnabel aff006;  Susanta K. Behura aff006;  Stephanie D. McKay aff008;  Jeremy F. Taylor aff006;  Flavia L. Lopes aff001
Působiště autorů: São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba, São Paulo, Brazil aff001;  Natural and Human Sciences Center, ABC Federal University, Santo André, São Paulo, Brazil aff002;  Genomics and Expression Laboratory, University of Campinas, Campinas, São Paulo, Brazil aff003;  Brazilian Bioethanol Science and Technology Laboratory (CTBE), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, São Paulo, Brazil aff004;  National Center for High Performance Computing (CENAPAD-SP), University of Campinas, Campinas, São Paulo, Brazil aff005;  Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America aff006;  Informatics Institute, University of Missouri, Columbia, Missouri, United States of America aff007;  Department of Animal and Veterinary Sciences, University of Vermont, Burlington, Vermont, United States of America aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222329

Souhrn

Methylation patterns established and maintained at CpG sites may be altered by single nucleotide polymorphisms (SNPs) within these sites and may affect the regulation of nearby genes. Our aims were to: 1) identify and generate a database of SNPs potentially subject to epigenetic control by DNA methylation via their involvement in creating, removing or displacing CpG sites (meSNPs), and; 2) investigate the association of these meSNPs with CpG islands (CGIs), and with methylation profiles of DNA extracted from tissues from cattle with divergent feed efficiencies detected using MIRA-Seq. Using the variant annotation for 56,969,697 SNPs identified in Run5 of the 1000 Bull Genomes Project and the UMD3.1.1 bovine reference genome sequence assembly, we identified and classified 12,836,763 meSNPs according to the nature of variation created at CpGs. The majority of the meSNPs were located in intergenic regions (68%) or introns (26.3%). We found an enrichment (p<0.01) of meSNPs located in CGIs relative to the genome as a whole, and also in differentially methylated sequences in tissues from animals divergent for feed efficiency. Seven meSNPs, located in differentially methylated regions, were fixed for methylation site creating (MSC) or destroying (MSD) alleles in the differentially methylated genomic sequences of animals differing in feed efficiency. These meSNPs may be mechanistically responsible for creating or deleting methylation targets responsible for the differential expression of genes underlying differences in feed efficiency. Our methyl SNP database (dbmeSNP) is useful for identifying potentially functional "epigenetic polymorphisms" underlying variation in bovine phenotypes.

Klíčová slova:

Biology and life sciences – Cell biology – Chromosome biology – Chromatin – Chromatin modification – DNA methylation – Genetics – Epigenetics – DNA modification – Gene expression – Gene regulation – DNA – Genomics – Genome analysis – Genomic databases – Genetic loci – Alleles – Molecular genetics – Biochemistry – Nucleic acids – Organisms – Eukaryota – Animals – Vertebrates – Amniotes – Mammals – Bovines – Cattle – Ruminants – Computational biology – Molecular biology – Research and analysis methods – Database and informatics methods – Biological databases


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