Lecture 15 – epigenetics
I. Some genetic effects are not mediated by changes in DNA sequence
A. epigenetics –
1. can be mediated by protein expression
2. often mediated by DNA/histone modification
3. stably maintained through cell division
II. Examples of epigenetic effects:
A. cell differentiation, eg. muscle cell differentiation
- differentiating muscle expresses myoD
B. genomic imprinting
1. What is it?
- copy of gene inherited from one parent is silenced
2. How? DNA methylation
3. Why? competition in utero
- only mammals
- females of many species have multiple mates
- male’s interest that his offspring biggest but female’s interest that
offspring not too big
- predicts that
imprinted genes
should regulate
growth, often but not
always true
4. eg. Mouse
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5. human: Prader-Willi vs Angelman syndromes
- Prader-Willi: mild mental retardation, obesity, diabetes
-Angelman: behavioral disorder, mental retardation
C. Position effect variegation
1. Position of gene on
chromosome affects its
expression
- translocation, inversion and
deletion all put gene in
different chromosomal context
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2. Variegation is mosaic effect where gene expressed in some cells, but not in
others
D. X chromosome inactivation
1. What is it? – in XX, one X is largely silenced
2. How? RNA interacting with DNA, DNA methylation, histone modification
3. Why? Balances X-linked gene expression in males and females
E. prions
1. Creutzfeldt-Jakob disease
- progressive neurodegeneration
- Kuru – one form, transmitted via cannibalism
2. scrapie – similar disease in sheep, scratch excessively
- neurodegeneration and death
3. mad cow disease (BSE – bovine spongiform encephalopathy)
- scrapie apparently transmitted to cows be feeding infected sheep parts
- EU forced Britain to destroy 4.7 million cows, cost $12, billion dollars
- BSE has been detected in US
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4. vCJD (variant Creutzfeldt-Jakob disease)
- transmitted to humans through consumption of infected beef
- in England, 100+ deaths so far
5. transmission?
- apparently no nucleic acid involved
- treatment with nuclease, radiation do not kill infectivity
- treatment with protease does
- seems to be transmitted via altered protein
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