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Human Biology
Stephen Wright

LECTURE 21 Epigenetics above the genome Effects of diet, X chromosome inactivation, and parental imprinting Genotype = phenotype in TWINS Even with monozygotic twins, there are still subtle differences o Differences may become more apparent as they age, especially in terms of health Mice All genetically identical Heterozygous for this allele These differences due to epigenetic changes Heritable modificationsChanges in gene function not due to changes in underlying baseline DNA Changes in gene expression created by o DNA methylation Occurring at CpG dinucleotides Results in repression of gene expression o Covalent modification of histone Histones modified by several different processes Lead to repression or activation of transcription o Recruitment of chromatin modelling complexes or specific variants of histones o Non-coding RNAs Result in transcriptional silencing Epigenetic and these mechanisms cause coat colour differences btw mice o Agouti gene is pleiotrophic gene Implicated in MANY traits, including coat colour, viability, obesity Fat mice also prone to diabetes and cancer Changes can be influenced by environment Retrotransposon inserted upstream of normal wildtype agouti promoter Retrotransposon has inserted its own cryptic promoter Promtoter then activates expression of agouti ectopically So turned on all the time Mice with viable yellow alleles have constant expression of this agouti viable allele o Results in yellow coat colour, susceptibility to heart disease, etc. bigger in size UNMETHYLATED retrotransposon Misregulates following gene so constantly on Methylation of transposon results in silencing of gene Agouti is under normal developmental controls Normal agouti promoter is turned on so have normal developmental expression o Methylation of this retrotransposon results in silencing and get wildtype phenotype o So what if feed yellow mothers with high methyl donor foods Yellow mice then give rise to offspring that are agouti o A mothers diet during pregnancy is important to overall phenotype in offspring Epigenetic changes can also be made in humans
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