Variation and Mutation

Question 1

What are the types of genetic variation?

Answer 1

1. Single nucleotide polymorphisms (SNPs) 2. Indels (insertions and deletions)
2. Copy number variations (CNVs)
3. Structural rearrangements

Question 2

Define polymorphisms

Answer 2

Two or more alleles of a gene, common in a population

Question 3

How can SNPS be detected?

Answer 3

DNA-DNA hybridisation techniques

Question 4

How can indels be analysed?

Answer 4

PCR and gel electrophoresis

STRS are multi allelic

Question 5

Describe genetic variations affect on phenotype

Answer 5

Intergenic region
• oftenno phenotypic effect - silent
Non-coding
regions of a gene
(introns,
promoter, UTRs)
• maybesilent
• Mayaffectgene expression
Protein-coding
region of a gene
• mayhavevarious
effects...

Question 6

Effect of base substitutions in coding regions?

Answer 6

Silent, Neutral, Mis-sense, nonsense

Question 7

How do indels affect protein function?

Answer 7

Frameshifts

Question 8

Describe mutations

Answer 8

an organism containing such an allele is termed
a mutant
• the normal allele/organism is termed wild type • mutantsareveryusefulforgenetics

Question 9

Describe mendelian disease?

Answer 9

Variation in a single gene is necessary and sufficient to cause disease
More than 1000 such genes known in humans
 Most of these diseases are rare

Question 10

Describe phenotypic effect

Answer 10

Much genetic variation has no effect, some single base variation has a profound effect

Question 11

How do cells prevent mutation

Answer 11

Proofreading DNA polymerase(s)
• Postreplication mismatch repair
• DNA repair by homologous recombination
• Cell cycle checkpoints

Question 12

What are the environmental factors that affect mutations?

Answer 12

Radiation or chemical mutagens

Question 13

Intercalating agents

Answer 13

planar molecules
insert between base pairs
• frameshift mutations

Question 14

Base analogues

Answer 14

incorporated into DNA in place of normal base • mis-pair
•  base substitutions
e.g. 5-bromouracil
• analogue of thymine
• but can base pair also with guanine:

Question 15

Base modifying agents

Answer 15

•covalently alter a base causing it to mispair •  base substitutions
Deaminating agents remove amino (-NH2) groups Hydroxylating agents add hydroxyl (-OH) groups Alkylating agents add alkyl (-CH3 or -CH3CH2) groups
• e.g.ethylnitrosourea(ENU)

Question 16

Alkylating agents

Answer 16

• So ENU converts G to A
• MMS act similarly, but by addition of a methyl group
• Other types of single-base mutation can be caused – e.g. ethylation of thymine leads to T-AC-G

Question 17

Mutations in coding regions

Answer 17

Wildtypegenes-functionalproteins
• Mutant genes - often non-functional proteins or unstable proteins
• Therefore in diploids most mutations are recessive
• This is why many mutations are lethal in haploid or
homozygous diploid
• Some mis-sense mutations are conditional lethal:

Question 18

Temperature sensitive mutations

Answer 18

mutant protein is less stable at non-permissive temperature

• very useful for studying essential cell functions • e.g.yeast ts mutants:

Question 19

Mutant selection

Answer 19

Selection is often used by geneticists to isolate rare mutants Especially useful with microbes, after mutagenesis