Genetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease

0437800 - FGÚ 2015 RIV US eng J - Článek v odborném periodiku
Johnson, M.D. - Mueller, M. - Adamowicz-Brice, M. - Collins, M. J. - Gellert, P. - Maratou, K. - Srivastava, P. K. - Rotival, M. - Butt, S. - Game, L. - Atanur, S. S. - Silver, N. - Norsworthy, P. J. - Langley, S. R. - Petretto, E. - Pravenec, Michal - Aitman, T. J.
Genetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease.
PLoS Genetics. Roč. 10, č. 12 (2014), e1004813. ISSN 1553-7404. E-ISSN 1553-7404
Grant CEP: GA ČR(CZ) GAP301/10/0290; GA MŠMT(CZ) LL1204; GA MŠMT(CZ) 7E10067
Institucionální podpora: RVO:67985823
Klíčová slova: cardiac methylome * genetic control of CpG methylation * epigenetic * rat
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 7.528, rok: 2014

Methylation of genomic DNA at cytosine residues is an important epigenetic modification that is associated with developmental processes, carcinogenesis and other diseases. Genome-wide methylation differences between individuals and the extent to which these differences depend on inter-individual variation in the primary DNA sequence are poorly characterised. To address those questions we have determined and compared the genome-wide methylation patterns in heart tissue of two inbred rat strains. Comparison of methylation differences between genetically identical animals from the same strain and differences between animals from different strains allowed us to quantify association of epigenetic and genetic differences. We show that differences in an individual’s germline DNA sequence are important determinants of the variability in methylation between individuals. The observed variation in methylation was strongly associated with genetic variation close to differentially methylated sequences explaining almost 60% of the difference in methylation observed at these locations between the two rat strains. Comparison with previous reports shows that the identified patterns of cytosine regulation are highly conserved across animal species and more widely between plants and animals
Trvalý link: http://hdl.handle.net/11104/0241347