1 - Fundamental Molecular Biology

Question 1

What is a mutation and net mutation?

Answer 1

A change in the genetic material of a cell/virus - not all heritable, can be due to radiation.
Net mutation = DNA damage minus repair.

Question 2

What is the rate and basis of spontaneous mutations?

Answer 2

• Occur at very low rate
• Required by natural selection to generate genetic differences
• Arise from replication/repair errors, by-product of metabolism, mutagens and ionising radiation.

Question 3

What do random mutations effect?

Answer 3

Mainly unimportant regions (silent) like between genes and exons.
This means they do not affect phenotype, but can affect key functional residues and regulatory regions.

Question 4

What are the types of point and frameshift mutations?

Answer 4

Point - none, missense (aa), nonsense (stop).
Frameshift - INDELs (insertion or deletion).

Question 5

What does most mutations being recessive mean?

Answer 5

They can only affect homozygous genotypes as recessive mutations require inbreeding - two carriers breeding is only way. It is also more common for loss of function (damage) than and advantageous change.

Question 6

What is albinism?

Answer 6

The failure to convert tyrosine into melanin, phenotype is caused by lowered production of product.
> Mutation in OCA1

Question 7

What is cretinism?

Answer 7

Lowered production of product.

Question 8

What is PKU?

Answer 8

Treated via low phenylalanine diet - gene encodes phenylalanine hydroxylase and phenotype is caused by build-up/excess of substrate.

Question 9

What is alkaptonuria?

Answer 9

Dark urine - build-up/excess of substrate.

Question 10

What is the level of enzyme activity in recessive mutations?

Answer 10

Less or no activity.

Question 11

How are mutations passed on and what does this mean?

Answer 11

Passed on via germline cells - these differentiate into somatic cells, which are genetic dead ends and disposable to natural selection - hence the rate of mutation is higher in soma.

Question 12

How do dominant mutations arise (3)?

Answer 12

1. Increase in enzyme activity
2. Higher protein production
3. New enzyme function

Question 13

What is achondroplasia?

Answer 13

• Dwarfism, autosomal dominant
• Non-conservative missense mutation
• Slows limb growth
• FGF more active

Question 14

What is Huntington’s Disease?

Answer 14

• Autosomal dominant
• Longer CAG repeat causes toxic protein
• Number of repeats can increase over time so is a progressive disease

Question 15

What are de novo mutations?

Answer 15

They are new and not from parents germline.

Question 16

What are orthologs?

Answer 16

• By common descent
• Probably have same role/function
• Infers interchangeable sequences

Question 17

What are paralogs?

Answer 17

• By duplication
• Differ in roles/functions
• Model organisms

Question 18

What is homology?

Answer 18

Biological features including genes and their products that are descended from a feature present in a common ancestor.
- Can explain genomic evolution.

Question 19

What are INDELS?

Answer 19

Insertion or deletion mutations which are common and small. Affect protein product if they occur in exons, but not gene function as they occur outside genes, introns etc.

Question 20

What are VNTRs?

Answer 20

• Variable number of tandem repeats aka micro/mini-satellites.
• Stable (passed down)
• Micro seen in Huntington’s

Question 21

What are CNVs?

Answer 21

Copy number variants which are common in chromosome segments.

Question 22

What is the difference between a variant and a polymorphism?

Answer 22

Mutant allele has frequency of….
Variant - <1%
Polymorphism - >1%

Question 23

What is the molecular definition of evolution?

Answer 23

A change in the allele frequency over time in a gene pool.

Question 24

What are SNPs?

Answer 24

Single nucleotide polymorphisms - affect protein product if inside reading frame, do not cause phenotype as they occur outside genes, introns etc.

Question 25

What is the Hardy-Weinberg equilibrium?

Answer 25

If allele frequency is at equilibrium, then the observed genotype ratios will equal the predicted values of the H-W equation.
By using a pair of allele frequencies, we can predict the diploid genotype frequencies that keep allele frequency constant from one generation to the next - no evolution will occur.
P = A
q = a
2pq = Aa

Question 26

When will allele frequencies be at equilibrium?

Answer 26

If they do not change with time, then the genotype frequencies will also stay at constant predicted values = equilibrium.

Question 27

What does H-W assume (for no evolution to be occurring)?

Answer 27

• Alleles are stable
• From large homogenous populations
• Random mating
• All genotypes equally fit