45. Molecular & Genomic Epidemiology of Infections

Question 1

What is molecular epidemiology?

Answer 1

A resolved measure (diversity) of differences (variables) that determines:
•Disease distribution in time and place
•Disease transmission
•Disease manifestation
•Disease progression

Question 2

How much diversity? - single, additive, multiple weighting

Answer 2

•Single Weighting - Presence or absence
•Additive Weighting - Combination of single tests
•Multiple Weighting - Genomic factors
- Factoral ~ Presence or absence of a gene/base/s change
in genome/gene relative to location in the genome
- Functional ~ Type of substitution (synonymous/non synonymous )
- Temporal ~ Mutation rate (time since the last alteration)

Question 3

Types of mutations in relation to their functions.

Answer 3

• Silent : Mutations that are Intragenic (between genes) or Synonymous (not altering coding)
• Non-Synonymous: Substitutions causing coding to be altered
• Corruptive:
• Deletions or Insertions (disrupting coding frame)
• Creation of STOP codons (truncation)
• Corruption of STOP codons (elongation)
• Corruption of CONTROL sequences (eg. promoters

Question 4

Antigenic drift

Answer 4

Antigenic drift is the same antigen changing its sequence base by base

Some mutations have more influence on Ab binding affinity than others

Herd immunity (after large vaccination program) kills most but also selects for escape mutants that maintain the drift

Question 5

What are the factors affecting the speed of the ‘Molecular Clock’?

Answer 5

• Bacterial replication rate
• DNA or RNA polymerase proof reading fidelity
• Selection pressure from the host or environment

• Degree of redundancy in the genome ~ multiple copies of a single gene in the genome allow for mutations in one copy without compromising overall functionality
Movement or recombination within genome may not effect phenotype

• Transmission rate

Question 6

In what case will high sequence mutation rate not affect the pathogenicity?

Answer 6

Antigenic drift

Question 7

Which genes change the most?

Answer 7

Hyper-variable genes change more rapidly than conserved genes but conserved genes are more likely to be associated with phenotype and virulence

Not all changes are new
Some may revert BACK to an older profile (convergent evolution)

Large and rapid changes are rare
but often lead to escape from existing herd protection

Question 8

In which case will genes be replaced completely?

Answer 8

Antigenic shift is a sudden replacement of an antigen by recombination with another viral type that has evolved separately (either in another animal or another human population). New types will not be protected against by previous infection or vaccination - leading to new epidemics.