MCBG Session 14 - DNA & Mutations Flashcards
What is a mutation?
What is mutagenesis?
- A heritable alteration in a gene or chromosome including the process that produces this alteration.
- The process of mutation generation
What is a transposable element and how does it cause a spontaneous mutation?
They are specific repetitive DNA sequence that move (transpose) also known as jumping genes which can cause mutations.
What is the difference between a transition and transversion single nucleotide polymorphism?
Transition = change to the same type of base (e.g.: purine to purine) Transversion = change to different type of base (e.g.: purine to pyrimidine)
What are the (4) possible consequences of SNP’s + the type of mutation that causes them?
- Change in gene product (missense)
- Change in the amount of gene product (mutations affecting regulatory sequences)
- Change in polypeptide length (frameshift/nonsense)
- No effect (silent/synonymous)
What is a missense mutation and the consequences of it?
What is a nonsense mutations and the consequences of it?
A missense mutation is when a SNP results in different amino acid in the polypeptide chain, which can result in a different phenotype - * change in gene product *
E.g.: Glu > Val mutation in Hbb leading to sickle cell anaemia.
A nonsense mutation is when a stop codon is coded for - consequence depends on where this mutation occurs but will cause premature chain termination + change the polypeptide length
What is a silent/anonymous mutation?
When a SNP does not affect the amino acid sequence therefore there is no phenotypic change.
What is a frameshift mutation?
A frameshift involves an insertion or deletion of nucleotides (in multiples other than 3) that results in a change to the reading frame, therefore all bases downstream of this mutation are not read correctly.
What kind of mutations change the amount of gene product produced?
Mutations affecting regulatory sequences (e.g.: promoter region/terminator region/TATA box).
How do trinucleotide expansions occur?
Give an example of how this can cause disease.
- Via fork slippage (see earlier lecture)
- CAG repeats in HTT gene leads to polyglutamine repeats in Huntingtin gene, leading to Huntington’s disease.
What kind of chromosomal abnormalities can occur when mutations occur?
- Numerical abnormalities (change in number)
- Structural abnormalities (change in structure)
What is the difference between balanced and unbalanced chromosomal abnormalities?
- Balanced = no genetic information lost and/or no phenotypic changes
- Unbalanced = Just not balanced/there is information lost or a phenotypic change
What is polyploidy and aneuploidy and how are they caused?
Polyploidy = Gain of haploid set of chromosomes (for each chromosome). Most common cause is polyspermy which causes ~15% of all miscarriages and occurs in ~2-3% of all pregnancies.
Aneuploidy = Loss or gain of whole chromosomes, e.g: monosomies or trisomies, caused by meiotic non-disjunction - e.g.: trisomy 21. (monosomies usually not viable for life).
What is mosaicism and how is it caused?
Presence of two or more cell lines in an individual. Can be throughout the body or tissue specific.. Caused by mitotic non-disjunction.
What is reciprocal translocation?
What are the consequences of this?
- A chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched.
- Quadrivalent forms, 6 possible outcomes (4:2 unbalanced)
- Main complication is passing on unbalanced chromosomes (have information missing information/changed phenotype).
What is Robertsonian translocations and the consequences of this?
When 2 acrocentric chromosome fuse - Robertsonian chromosome acts as one chromosome - therefore chromosome count is 45.
Trivalent will form, with 6 possible outcomes. Risk of aneuploidy, both monosomy or trisomy.
