Causes and Effects of Genetic Variation Flashcards
How are bases, large blocks of DNA and chromosomes visualised?
1 - Bases: Sequencing.
2 - Large blocks of DNA: Fluorescence in situ hybridisation (FISH).
3 - Chromosomal: Light microscopy.
Describe the Sanger method of DNA sequencing.
1 - A section of DNA to be analysed is amplified by PCR.
2 - A set of fragments of that DNA that differ in length by a single base are produced.
3 - The fragments are separated by size, and the bases at the end of each fragment are identified, recreating the sequence.
List 4 endogenous mechanisms that have the potential to cause DNA damage.
1 - Depurination.
2 - Deamination.
3 - Reactive oxygen.
4 - Methylation of cytosines.
What is depurination?
The spontaneous fission of the link between a purine base and the ribose sugar, causing a deletion mutation.
How can deamination cause a mutation?
- The loss of the amine group from cytosine, creating uracil.
- Also causes substitution for an arginine in the new strand.
How can methylation cause a mutation?
Methylation of CpG dinucleotides causes spontaneous deamination of 5-methylcytosine to thymine (forming a TpG dinucleotide).
What are CpG dinucleotides?
Regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide (on the same side of the strand).
What often results from methylation of CpG dinucleotides?
Generation of a stop codon (CGA -> TGA).
How can UV light cause DNA damage?
By forming cross links between thymines on a DNA strand to form dimers.
How can environmental chemicals cause damage to DNA?
1 - By interpolating into DNA.
2 - By causing breaks to the DNA.
What molecule is responsible for correcting DNA replication errors.
How does it do this?
- DNA polymerase.
- During DNA replication, it adds a base, checks it, excises it if it is wrong then moves on.
What is homologous recombination?
The process of repairing a DNA double strand break by using the homologous DNA strand.
How is damage to DNA due to ionising radiation and reactive oxygen species corrected?
1 - By homologous recombination.
2 - By end-joining broken ends.
Describe the process of end-joining broken ends.
Nuclease breaks the regions of DNA between the breaks in both strands so that they are broken to the same point and ligase joins the broken ends.
What is a missense mutation?
A mutation that alters the sequence of bases to produce a different sequence of amino acids.
What is a nonsense mutation?
A mutation that generates a stop codon.
What is the function of a spliceosome?
To removes introns from a transcribed pre-mRNA.
What might mutations at splice sites cause?
1 - Exon skipping (mutation to the acceptor site).
2 - Incorporation of the intron sequence into mRNA (mutation to donor site).
What are the names of the regions at the start and end of a splice site?
- Donor site (start).
- Acceptor site (end).
How do repeat sequences cause mutations?
Repeat sequences predispose to large deletions and duplications as they may cause slipped strand mispairing.
What is the effect of Huntington disease on the genome?
> 30 CAG repeats.
What is the effect of myotonic dystrophy on the genome?
> 34 CTG repeats.
What is the effect of fragile-X syndrome on the genome?
> 50 CGG repeats.
How might crossing over result in a mutation?
Unequal crossing over between repeat sequences may result in large deletions and insertions.
What is copy number variation?
Where the number of copies of the same gene varies between individuals.
What is a silent mutation?
A mutation that alters the sequence of bases but does not alter the sequence of amino acids.
