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Lecture

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Department
Biology
Course Code
BIO120H1
Professor
Jean Jiang Nash

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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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Description
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 www.notesolution.com
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