Wright Lecture 11: Mutations and Their Effect on Phenotype

Question 1

Mutation

Answer 1

Permanent change in the hereditary material: DNA or RNA

Question 2

Mutations occur in two types of cells

Answer 2

1. Somatic cells of multicellular organisms

2. Germ-line cells (sperm, eggs)

Question 3

Somatic cell mutation

Answer 3

Occurs in non-reproductive cells: liver, intestine, skin, etc
Spontaneous or induced by chemical/physical mutagen
Not inherited by offspring
Usually little or no affect on individual, but some can give rise to cancer

Question 4

Germ-line mutation

Answer 4

Occur in cells of ovary or testis that give rise to gametes
Meiosis and sexual reproduction allow germ-like mutations to be passed to about half of members of next generation: these offspring will carry the mutation in all their genes

Question 5

Chromosomal mutation

Answer 5

1. Affected number

2. Structural aberrations

Question 6

Aneuploidy

Answer 6

Caused by nondisjunction in meiosis

Monosomy, trisomy

Question 7

Down syndrome

Answer 7

Trisomy 21

Caused by nondisjunction in meiosis

Question 8

Structural aberration in chromosomes

Answer 8

Transactions, insertions, inversions, deletions

Question 9

Transposition of genes

Answer 9

Via transposable elements

Question 10

Point mutations

Answer 10

Alterations involving one or a few changes in DNA

1. Substitution of one base pair for another
2. Insertion or deletion of one or more base pairs

Question 11

Base pair substitution

Answer 11

Transitions: purine to purine
Transversions: purine to pyrimidine, or pyrimidine to purine
1. No affect on amino acid sequence
2. Missence (new amino acid)
3. Nonsense (stop)

Question 12

Insertion/deletion of one or more base pairs

Answer 12

1. Frameshift causing immediate nonsense (stop)
2. Frameshift causing extensive missense (new pattern of amino acids)
3. Insertion or deletion of 3 nucleotides (no frameshift, but extra or missing amino acids)

Question 13

Classifications of mutations

Answer 13

1. Transitions and transversions
2. Silent mutations
3. Missense mutations
4. Nonsense mutation
5. Frameshift mutation

Question 14

Transition

Answer 14

Purine to purine

Question 15

Transversion

Answer 15

Purine to pyrimidine, or pyrimidine to purine

Question 16

Silent mutations

Answer 16

No change in amino acid sequence of polypeptide

Question 17

Missence mutations

Answer 17

1. Neutral
2. Loss-of function
3. Gain-of function

Question 18

Neutral mutation

Answer 18

Alters amino acid sequence but has no affect on function of polypeptide

Question 19

Loss-of function mutation

Answer 19

Complete or partial absence of polypeptide function

Question 20

Gain-of function mutation

Answer 20

Completely new function for the polypeptide, or inappropriate spatial/temporal pattern in its expression

Question 21

Non-sense mutation

Answer 21

Stop codon usually resulting in a truncated polypeptide

Question 22

Frameshift mutation

Answer 22

Neutral or radical affect on phenotype owing to either a missense of nonsense mutation

Question 23

Reverse mutations

Answer 23

Second mutation that restores the function of polypeptide

True reversions or suppressor mutations

Question 24

Suppressor mutations

Answer 24

First mutation is suppressed by second mutation

1. Intragenic
2. Intergenic

Question 25

Intragenic suppressor mutations

Answer 25

In the same gene
Missense mutation alters a single codon, a second mutation at a different site in the same gene may restore original amino acid

Question 26

Intergenic suppressor mutations

Answer 26

In a different gene

ie. Mutation in activating protein makes pathway non-functional - cannot activate effector protein. New mutation in effector protein causes protein complex to now be functional
ie. Mutation in sequence causes stop codon. Mutation in tRNA causes Leu to be added to growing polypeptide instead, completing protein

Question 27

What causes mutations?

Answer 27

Spontaneous

Induced by physical and chemical agents

Question 28

Types of spontaneous mutations

Answer 28

1. Tautomeric shifts
2. DNA strand-slippage during DNA replication
3. Misalignment of homologous chromosomes during crossing over

Question 29

Tautomeric shifts

Answer 29

Base tautomers
Proton shift, causing anomalous base-pairing
C-A
T-G

Question 30

DNA strand-slippage during DNA replication

Answer 30

1. Newly synthesized strand loops out, resulting in addition of one nucleotide on the new strand
2. Template strand loops out, resulting in the omission of one nucleotide on the new strand

Question 31

Misalignment of homologous chromosomes during meiosis

Answer 31

One cross over product contains and insertion and the other has a deletion