Lecture 15: Epigenetics: Identical Twins are Not
1. Regulation of gene expression
Pack and organize eukaryotic DNA
Small +ve charged basic proteins attracted to –ve charged
phosphate in eukaryotic DNA chromosomes
3. Reasons why, if identical twin women have sons with identical twin
men, the sons will not be identical.
DNA from mom and dad is different
Meiosis make different gametes (sexual recombination)
4. What does more than 50% heritability mean?
At higher risk than unrelated people
Doesn’t mean 50% ≤ chance of getting disease
5. Characteristics that would, and would not, be different between
monozygotic ("identical") twins.
Random mutations (environmental mutagens)
Random X chromosome inactivation (females) by noncoding RNA
6. Process of random X inactivation leading to genetic mosaicism.
Inactivate genes on either (maternal/mom or paternal/dad x)
o Don’t need twice the product of those genes
Condensation process folds, packs chromatin of inactive x chromosome into dense chromatin (barr body)
o Inactivation occurs during embryonic development after divided into 100 cells
All descendants of the cell will be inactive as well
In humans, female skin cells are inactive or active but can’t tell because skin pigments aren’t on
Compare genomes of twins through digestion by restriction enzymes
o Bands in the same place = same nuclear DNA and fingerprint = twins
o Digest inactive x of diff alleles are detectable by size to reveal which chromosome is inactive
Long allele = big piece; small allele = small piece
If only small x is inactivate than you get the big piece only (only one type inhibited)
If random 50/50, get big and small pieces
7. How a mosaic is different from a heterozygote in recessive sex linked.
Whichever x chromosome is active, that allele will be active
Inactivation of either x has little effect since dominant allele is active enough or it may produce patches
o Milder symptoms if dominant sex linked allele is sometimes inactivated
o What about homozygous sex linked, dominant sex-linked?
o Skewed/non-random x inactivation lowers where dominant sex-linked gene all inactivated?
8. Role of Xist RNA
Xist RNA binds along the inactive X chromosome, silencing most genes
Normally chromosomes are opened and accessible to RNA polymerase (transcription factors)
Xi specific transcription only made from inactive x
o Coats chromosome and DNA keeps away from transcription factories
o Xist RNA directly bind with protein not complementary base pairing to keep it inactive
If Xist gets translated chromosome shuts down
o But tsix (antisense – complementary strand) gets transcribed the other way on bottom strand
o Expression of tsix shuts off Xist (not protein coding genes/ noncoding RNA regulate expression) 9. Function of nucleosomes in chromatic structure.
When xist RNA interacts with the chromosome its compacting
o DNA in form of chromatin associated with protein (histones) nucleosomes (histones + DNA)