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Table 1 Examples of genes and specific sequences that support or reject the hypothesis that genotype predisposes transgenerationally inherited epitype and phenotype

From: The influence of DNA sequence on epigenome-induced pathologies

Genes/Sequences affected Genotype contribution Known aberrant epitype/gene expression Phenotype of epimutation or epigenetic change Species Supports/rejects hypothesis
A. Direct analysis of trans-generational inheritance
1. RYR1 ryanodine-receptor Unknown Cytosine hypermethylation/silenced hyperthermia, core myopathies human Rejects
2. MLH1 (Homolog of mismatch repair protein MutL) Allele specific silencing Cytosine hypermethylation/silenced Colorectal or endometrial cancers human Weakly supports
3. AGOUTI (paracrine signaling peptide) Alleles with retrotransposon Cytosine hypomethylation/activation Yellow, obese mouse Supports
4. AXIN1-FUSED Alleles with retrotransposon Cytosine hypomethylation, histone acetylation/activation Axin-fused kinked tail mouse Supports
5. CNR Colorless Non-Ripening Native CpG rich region Cytosine hypermethylation/silenced Carotenoid synthesis tomato Rejects
6. CYC – cycloidea (transcription factor) Native CpG rich region and possible genotype difference Cytosine hypermethylation/silenced Floral morphology Linaria vulgaris Likely supports
7. H3K4Me2 demethylase None identified Histone H3 lysine4 dimethylation retained causing gene activation Germ line immortality Caenorhabditis elegans Likely rejects
8. Quantitative epigenetic trait loci ( for example, many loci) DNA DEMETHYLATION1 ddm1/ddm1 restored to DDM1/DDM1 Cytosine re-methylation and re-silencing Flowering time and plant height Arabidopsis thaliana Supports
9. Reprogramming of 5Me C by dsRNA siRNA, miRNA, piRNA, and other dsRNAs Cytosine re-methylation and re-silencing Complex, molecular, and developmental Arabidopsis, mice Supports
10. Somatic cell nuclear transfer Genome-wide Cytosine re-methylation and histone modifications Embryonic and fetal development Mice, sheep, pigs, cows Mostly supports
B. Indirect analysis using sequence conservation and gene duplication
1. RRRRRYYYYY repeat throughout the genome 10.5 bp repeats position most nucleosomes N.M. N.M. Diverse animal species Supports
2a. Histone H2AZ in >1,000 nucleosomes 10 bp repeat of G + C and A + T rich dinucleotides Histone H2AZ variant positioning Potentiated for expression. N.M. Yeast, human, Arabidopsis Supports
2b. H2AZ in FLC, MAF4, MAF5 Subfamily of three recently duplicated MADS box genes Bimodal distribution of H2AZ enriched nucleosomes/activated Altered flowering time and gene expression Arabidopsis Supports
3. Histone CenH3 in ~100,000 nucleosomes 10 bp repeat of AA or TT dinucleotides Histone CenH3 variant positioning Essential for chromosomal segregation. N.M. maize Supports
4. Blood plasminogen genes (PMGs) Cytosine methylation in 208 bp region upstream of four PMG genes N.M. Demethylation activates four linked PMG alleles genes in liver. Methylation silences in other organs. human Supports
5. 1600 segmental duplications Duplicated gene sequences Several different histone side chain modifications Duplicate alleles generally silenced relative to active parental allele. N.M. human Rejects
6. HoxD cluster Five gene duplicated HOXD genes Modestly conserved nucleosomal and H3K4Me2 patterns N.M. human Supports
7. DNA loops and microsatellites Concatenated DNA loops and trans-chromosomal contacts Binding by HMG box proteins to control gene expression N.M. mammals Modestly supports
  1. N.D., no data; N.M., not based on a mutational study.