Notes taken during lecture

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29 Mar 2011
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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
oDifferences 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 modifications/Changes in gene function not due to changes in underlying baseline
DNA
Changes in gene expression created by
oDNA methylation
Occurring at CpG dinucleotides
Results in repression of gene expression
oCovalent modification of histone
Histones modified by several different processes
Lead to repression or activation of transcription
oRecruitment of chromatin modelling complexes or specific variants of histones
oNon-coding RNAs
Result in transcriptional silencing
Epigenetic and these mechanisms cause coat colour differences btw mice
oAgouti 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
oResults in yellow coat colour, susceptibility to heart disease,
etc. bigger in sizeUNMETHYLATED 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
oMethylation of this retrotransposon results in silencing and get wildtype phenotype
oSo what if feed yellow mothers with high methyl donor foods
Yellow mice then give rise to offspring that are agouti
oA mother’s diet during pregnancy is important to overall phenotype in offspring
Epigenetic changes can also be made in humans
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Document Summary

Effects of diet, x chromosome inactivation, and parental imprinting. Even with monozygotic twins, there are still subtle differences: differences may become more apparent as they age, especially in terms of health.  heritable modifications/changes in gene function not due to changes in underlying baseline.  changes in gene expression created by: dna methylation.  results in repression of gene expression: covalent modification of histone.  lead to repression or activation of transcription: recruitment of chromatin modelling complexes or specific variants of histones, non-coding rnas. Epigenetic and these mechanisms cause coat colour differences btw mice: agouti gene is pleiotrophic gene. Implicated in many traits, including coat colour, viability, obesity. Fat mice also prone to diabetes and cancer.  retrotransposon inserted upstream of normal wildtype agouti promoter: retrotransposon has inserted its own cryptic promoter, mice with viable yellow alleles have constant expression of this.

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