Mechanisms of genetic change
Describe replication slippage
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Replication slippage can lead to misalignment of the template or newly synthesised strand and results in unequal
daughter strands
Slippage on the newly synthesised strand: the strand momentarily
separate and a nucleotide loops out, when the strands come back
together this results in an insertion as RNA polymerase continues to
transcribe the template. Once transcription has completed the
daughter strand will be longer than the template. So that in the next
round of replication the repeat is longer
Slippage on the template strand: the strand momentarily separate
and a nucleotide on the template strand loops over. This results in a
deletion as RNA polymerase continues to transcribe from the
template. The daughter strand will be shorter than the template. In
the next round of replication the repat sequence will be shorter
Explain the generation of tandem repeats
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Replication slippage can cause the insertion/deletion of several nucleotides which can generate tandem repeats
and also cause trinucleotide expansion
How does expansion of trinucleotide repeats occur?
1. The two strands separate and replicate
2. In the course of replication a hairpin structure forms on the newly synthesised strand (complimentary base
pairing)
3. this causes part of the template strand to be replicated twice and increasing the number of repeats on the newly
synthesised strand
4. the two strands of the new DNA molecule separate
5. and the strand with the extra CAG repeats serves as a template for replication
6. the resulting DNA molecule contains 5 additional copies of the CAG repeat
Example where trinucleotide expansion can lead to disease?
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Huntington disease: abnormal numbers of repeat of CAG (37-121 repeats)
Jacobsen syndrome: abnormal number of repeats of CGG (100-100 repeats)