Causes and Effects of Genetic Variation

Question 1

How are bases, large blocks of DNA and chromosomes visualised?

Answer 1

1 - Bases: Sequencing.

2 - Large blocks of DNA: Fluorescence in situ hybridisation (FISH).

3 - Chromosomal: Light microscopy.

Question 2

Describe the Sanger method of DNA sequencing.

Answer 2

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.

Question 3

List 4 endogenous mechanisms that have the potential to cause DNA damage.

Answer 3

1 - Depurination.

2 - Deamination.

3 - Reactive oxygen.

4 - Methylation of cytosines.

Question 4

What is depurination?

Answer 4

The spontaneous fission of the link between a purine base and the ribose sugar, causing a deletion mutation.

Question 5

How can deamination cause a mutation?

Answer 5

• The loss of the amine group from cytosine, creating uracil.
• Also causes substitution for an arginine in the new strand.

Question 6

How can methylation cause a mutation?

Answer 6

Methylation of CpG dinucleotides causes spontaneous deamination of 5-methylcytosine to thymine (forming a TpG dinucleotide).

Question 7

What are CpG dinucleotides?

Answer 7

Regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide (on the same side of the strand).

Question 8

What often results from methylation of CpG dinucleotides?

Answer 8

Generation of a stop codon (CGA -> TGA).

Question 9

How can UV light cause DNA damage?

Answer 9

By forming cross links between thymines on a DNA strand to form dimers.

Question 10

How can environmental chemicals cause damage to DNA?

Answer 10

1 - By interpolating into DNA.

2 - By causing breaks to the DNA.

Question 11

What molecule is responsible for correcting DNA replication errors.

How does it do this?

Answer 11

• DNA polymerase.

- During DNA replication, it adds a base, checks it, excises it if it is wrong then moves on.

Question 12

What is homologous recombination?

Answer 12

The process of repairing a DNA double strand break by using the homologous DNA strand.

Question 13

How is damage to DNA due to ionising radiation and reactive oxygen species corrected?

Answer 13

1 - By homologous recombination.

2 - By end-joining broken ends.

Question 14

Describe the process of end-joining broken ends.

Answer 14

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.

Question 15

What is a missense mutation?

Answer 15

A mutation that alters the sequence of bases to produce a different sequence of amino acids.

Question 16

What is a nonsense mutation?

Answer 16

A mutation that generates a stop codon.

Question 17

What is the function of a spliceosome?

Answer 17

To removes introns from a transcribed pre-mRNA.

Question 18

What might mutations at splice sites cause?

Answer 18

1 - Exon skipping (mutation to the acceptor site).

2 - Incorporation of the intron sequence into mRNA (mutation to donor site).

Question 19

What are the names of the regions at the start and end of a splice site?

Answer 19

• Donor site (start).

- Acceptor site (end).

Question 20

How do repeat sequences cause mutations?

Answer 20

Repeat sequences predispose to large deletions and duplications as they may cause slipped strand mispairing.

Question 21

What is the effect of Huntington disease on the genome?

Answer 21

> 30 CAG repeats.

Question 22

What is the effect of myotonic dystrophy on the genome?

Answer 22

> 34 CTG repeats.

Question 23

What is the effect of fragile-X syndrome on the genome?

Answer 23

> 50 CGG repeats.

Question 24

How might crossing over result in a mutation?

Answer 24

Unequal crossing over between repeat sequences may result in large deletions and insertions.

Question 25

What is copy number variation?

Answer 25

Where the number of copies of the same gene varies between individuals.

Question 26

What is a silent mutation?

Answer 26

A mutation that alters the sequence of bases but does not alter the sequence of amino acids.