The framework for population epigenetic study

At present, understanding of DNA methylation at the population level is still limited. Here, we first extended the classical framework of population genetics, such as single nucleotide polymorphism allele frequency, linkage disequilibrium (LD), LD block and haplotype, to epigenetics. Then, as an example, we compared the DNA methylation disequilibrium (MD) maps between HapMap CEU (Caucasian residents of European ancestry from Utah) population and YRI (Yoruba people from Ibadan) population (lymphoblastoid cell lines). We analyzed the differences and similarities between CEU and YRI from the following aspects: SMP (single methylation polymorphism) allele frequency, SMP allele association, MD, MD block and methylation haplotype (meplotype) frequency. The results showed that CEU and YRI had similar distribution of SMP allele frequency, and shared many MD block region. We believe that the framework of population genetics can be used in the population epigenetics. The population epigenetic framework also has potential prospects in the study of complex diseases, such as epigenome-wide association study.

[1]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[2]  Wei Zhang,et al.  Linking the genetic architecture of cytosine modifications with human complex traits. , 2014, Human molecular genetics.

[3]  Wei Zhang,et al.  SCAN database: facilitating integrative analyses of cytosine modification and expression QTL , 2015, Database J. Biol. Databases Curation.

[4]  S. Horvath.  DNA methylation age of human tissues and cell types , 2013, Genome Biology.

[5]  W. Reik.  Stability and flexibility of epigenetic gene regulation in mammalian development , 2007, Nature.

[6]  Wei Zhang,et al.  Genome-Wide Variation of Cytosine Modifications Between European and African Populations and the Implications for Complex Traits , 2013, Genetics.

[7]  Lijun He,et al.  Identification of common genetic variants that account for transcript isoform variation between human populations , 2008, Human Genetics.

[8]  P. Avner,et al.  X-chromosome inactivation in mammals. , 1997, Annual review of genetics.

[9]  D. Balding.  A tutorial on statistical methods for population association studies , 2006, Nature Reviews Genetics.

[10]  Sharon R Grossman,et al.  Integrating common and rare genetic variation in diverse human populations , 2010, Nature.

[11]  M. Kobor,et al.  DNA methylation and healthy human aging , 2015, Aging cell.

[12]  Jim Stalker,et al.  A Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci , 2008, PLoS biology.

[13]  H. Saedler,et al.  Epigenetic changes in the expression of the maize A1 gene inPetunia hybrida: Role of numbers of integrated gene copies and state of methylation , 1990, Molecular and General Genetics MGG.

[14]  Jakob C. Mueller,et al.  Linkage disequilibrium for different scales and applications , 2004, Briefings Bioinform..

[15]  E. Birney,et al.  An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). , 2008, Genome research.

[16]  Marius A. Wenzel,et al.  Fine-scale population epigenetic structure in relation to gastrointestinal parasite load in red grouse (Lagopus lagopus scotica) , 2014, Molecular ecology.

[17]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[18]  G. Abecasis,et al.  A note on exact tests of Hardy-Weinberg equilibrium. , 2005, American journal of human genetics.

[19]  Peter A. Jones,et al.  The Role of DNA Methylation in Mammalian Epigenetics , 2001, Science.

[20]  Paul Haggarty,et al.  Population Epigenetics , 2017, Methods in Molecular Biology.

[21]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[22]  B. Stranger,et al.  Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics , 2011, Genetics.

[23]  R. Lewontin.  The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. , 1964, Genetics.

[24]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[25]  Matthew D. Schultz,et al.  Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants , 2011, Science.

[26]  Xiao Zhang,et al.  Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis , 2010, BMC Bioinformatics.

[27]  Joel N Hirschhorn,et al.  Genome-wide association studies: results from the first few years and potential implications for clinical medicine. , 2011, Annual review of medicine.

[28]  Matthew D. Schultz,et al.  Patterns of Population Epigenomic Diversity , 2013, Nature.

[29]  Carl T. Bergstrom,et al.  A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Maneesh Sud,et al.  A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing. , 2013, Blood.

[31]  Rudolf Jaenisch,et al.  Role for DNA methylation in genomic imprinting , 1993, Nature.

[32]  Luigi Ferrucci,et al.  GeMes, clusters of DNA methylation under genetic control, can inform genetic and epigenetic analysis of disease. , 2014, American journal of human genetics.

[33]  R. Shoemaker,et al.  Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. , 2010, Genome research.

[34]  L. Excoffier,et al.  Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. , 1995, Molecular biology and evolution.

[35]  W. G. Hill,et al.  Linkage disequilibrium in finite populations , 1968, Theoretical and Applied Genetics.

[36]  Karsten M. Borgwardt,et al.  Spontaneous epigenetic variation in the Arabidopsis thaliana methylome , 2011, Nature.

[37]  Debra A Schwinn,et al.  Epigenetic regulation of human α1d‐adrenergic receptor gene expression: a role for DNA methylation in Spl‐dependent regulation , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  Zachary A. Szpiech,et al.  Genome-wide association studies in diverse populations , 2010, Nature Reviews Genetics.