Mechanisms And Effects Of Mutations

Question 1

What kinds of alterations are there in sequence of bases in specific sections of DNA?

Answer 1

1. Single nucleotide polymorphism (common)
2. Small deletions/ duplications (few bases)

Question 2

Types of tandem repeats? 2

Answer 2

1. Microsatellites 2-3 base pairs
2. Minisatellites 10-60 base pairs

Question 3

Types of variation in genome

Answer 3

1. Alteration in sequence of bases in specific sections of DNA
2. Tandem repeats
3. Larger duplications/ deletions
4. Changes in number or structure of chromosomes

Question 4

Variation in genome can lead to

Answer 4

Altered effects of a protein
Difference in control of genes

Question 5

Genome variation can lead to (examples)

Answer 5

Normal human variation eye colour
Difference in response to medication
Influence the likelihood of disease (more common)
Directly the result of a genetic disease

Question 6

Three ways genome variant classified

Answer 6

1. Size
2. Frequency
3. Clinical effects

Question 7

What is a mutation?

Answer 7

An alteration or change in genetic material

Question 8

Causes of mutations?

Answer 8

Exposure to mutagenic agents
Spontaneously through errors in DNA replication/ repair

Question 9

How can polymorphism be non harmful

Answer 9

Sequence variant is in non functional DNA
Sequence variant within gene but doesn’t change aa
Sequence variant changed aa but doesn’t alter protein function

Question 10

Polymorphism?

Answer 10

Two or more possibilities of a trait on a gene

Question 11

SNP?

Answer 11

Single nucleotide polymorphism (most common type of variant)

To be called SNP base Change has to have frequency of less than 1%

Question 12

Example of SNP?

Answer 12

Change of C to a T
One of three patterns CC, CT, TT

Question 13

How an genome be examined?

Answer 13

Examine bases - sequencing/ microanalysis
Examine large blocks of DNA - FISH/ microanalysis
Chromosomal - light microscopy

Question 14

Steps of DNA sequencing

Answer 14

1. Amplify very small amounts of target DNA (usually by PCR)
2. DNA is used as a template to generate a set of fragments that
   differ in length from each other by a single base.
3. The fragments are then separated by size, and the bases at the end are identified, recreating the original sequence of the DNA.

Question 15

Why sequence DNA?

Answer 15

Determine exact POSITION of mutation

Determine the TYPE of mutation

Question 16

Next generation sequencing?

Answer 16

Whole molecule sequencing
Much faster and cheaper
Predict health, diagnosis, individualised med

Question 17

When do mutations occur?

Answer 17

1. During cell division
2. From intrinsic and extrinsic attacks on DNA

Question 18

What is reduction division

Answer 18

1 round of replication
2 rounds of division
(Meiosis)

Question 19

How does meoitic cell division cause human disease

Answer 19

Passed on to offspring
Heritable

Question 20

How does mitotic division cause disease

Answer 20

Somatic cells affected
Cancer/ non inheritable

Question 21

Endogenous mechanism

Answer 21

Originate from inside the body

Question 22

Endogenous mechanisms causing DNA damage

Answer 22

1. Depurination - spontaneous breakage of link between purine base and sugar. Loss of A or G.
2. Deamintion - C delaminates to U. Substitution of A on new strand.
3. Reactive oxygen - attack purine/ pyrimidine rings
4. Methylation of cytosines

Question 23

Methylation of cytosines?

Answer 23

High frequency of deamination of C to T
Common at CpG dinucleotides

Question 24

Extracellular agents causing DNA damage

Answer 24

1. Ultraviolet light - covalent linkage of adjacent Ts to form stable dimers. Stop DNA replication.
2. Environmental chemicals
3. Ionising radiation - breaks DNA

Question 25

G2 checkpoint?

Answer 25

Check if DNA replicated correctly before enters mitosis
Prevent passing mutations to daughter cells

Question 26

Methods of correcting DNA replication errors?

Answer 26

• Proof reading by DNA polymerase
• DNA mismatch repair system (back up)
• DNA double strand break repair

Question 27

Pathogenic mutations?

Answer 27

Occur in exons and in regulatory sequences in introns
Detection of a pathogenic mutation allows genetic testing for other family members and in some diseases influences clinical management

Question 28

Types of point mutations

Answer 28

Missense - change in singe base
Nonsense - change of aa to a stop codon. Creates truncated (short) protein.
Frameshift - insertions/ deletions/ duplications
Silent - degenerative. Doesn’t affect amino acid

Splice site - mRNA altered

Question 29

None sense mediated decay process

Answer 29

Degradation of truncated protein

Question 30

Splice site mutations

Answer 30

Alters mRNA
Site where introns are spliced from pre mRNA
GU donor sites
AG acceptor sites
Mutations at site causes site to be missed and acceptor site recognised causing removal of exon

Question 31

Copy number variants

Answer 31

Small arrays of triplet repeats in coding sequences of genes that are prone to expand in number and disrupt gene function

Question 32

Effects of Larger deletions/ insertions of copy number variants?

Answer 32

• Causes misalignment of chromosomes leading to unequal crossing over of non sister chromatids during meiosis
• deletions more severe
• clinical effects depend on genes involved and gene size

Question 33

What is spliceosome

Answer 33

The spliceosome precisely removes introns from pre-mRNA to generate mature messages (mRNA), a process referred to as pre-mRNA splicing. The spliceosome is essential for cell function and defective pre-mRNA splicing causes disease