A genomic atlas of systemic interindividual epigenetic variation in humans.

Autor: Gunasekara CJ; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Scott CA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Laritsky E; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Baker MS; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., MacKay H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Duryea JD; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Kessler NJ; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, The Gambia.; Department of Women and Children's Health, King's College London, London, UK., Hellenthal G; Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London, WC1E 6BT, UK., Wood AC; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Hodges KR; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA., Gandhi M; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA., Hair AB; Department of Pediatrics - Neonatology, Baylor College of Medicine, Houston, TX, USA., Silver MJ; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, The Gambia., Moore SE; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, The Gambia.; Department of Women and Children's Health, King's College London, London, UK., Prentice AM; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Keneba, The Gambia., Li Y; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Chen R; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Coarfa C; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. coarfa@bcm.edu., Waterland RA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. waterland@bcm.edu.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. waterland@bcm.edu.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2019 Jun 03; Vol. 20 (1), pp. 105. Date of Electronic Publication: 2019 Jun 03.
DOI: 10.1186/s13059-019-1708-1
Abstrakt: Background: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific.
Results: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues.
Conclusions: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.
Databáze: MEDLINE
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