Molecular And Genomic Epidemiology Of Infection

Question 1

What is molecular epidemiology?

Answer 1

A resolved measure (diversity) of variables that determines the genetic basis of disease, including variants within hosts and pathogens that influence infection, transmission and prevention.

Question 2

How can molecular epidemiology confirm outbreaks?

Answer 2

Inside institutions - did patient A get this pathogen from patient B?

In the community - who was the dna see and what i the likely source?

In the past - what has driven the geographical spread of important strains?

In the lab - Is this a outbreak or containment?

Question 3

How can molecular epidemiology be used to identify disease risks?

Answer 3

Shifts in virulence - are drug resistant strains on the rise? Has the incidence of annual infections increased?

Reservoirs of infection - new infection or recrudescence

Question 4

What is resolved diversity?

Answer 4

How much difference is enough?

Question 5

How do we determine which target to choose?

Answer 5

Based on functional characteristics
- classical biochemistry
- serology
- virulence

and Genomic characteristics
- DNA
- RNA

Question 6

How can we determine the diversity?

Answer 6

Single weighting - presence or abscence

Additive weighting - combination of single tests

Multiple weighting - genomic factors

Biochemical test - presence of 0157 antigen or verotoxin

Question 7

Describe FACTORIAL multiple copy number systems (Spoligotypng)?

Answer 7

1. PCR with RE reigon primers generates multiple length amplicons
2. hybridisation do labelled PCR product onto 43 space specific olignucleotides fixed on a membrane then visualise signal with RE probe

3.Result is a profile of the presence/absence of specific repeats at ONE locus

Question 8

Describe FACTORIAL multiple copy number systems (VNTR)?

Answer 8

Variable number of host tandem repeats

Result is a profile of the number of specific repeats at multiple genomic loci

Question 9

How can functional diversity arise?

Answer 9

Phylogenic progression (single base substitutions)

Question 10

What is a silent mutation?

Answer 10

Mutations that intragenic (between genes)

Synonymous (not altering codon)

Question 11

What are corruptive mutations?

Answer 11

Deletions or insertions

Creation of stop codons

Corruption of stop codons

Corruption of control sequences

Question 12

What is drift?

Answer 12

Gradual alteration in sequence

Question 13

What is antigenic drift?

Answer 13

Same antigen changing its sequence base by base

Question 14

What is antigen shift?

Answer 14

A sudden replacement of an antigen by recombination with another viral type that has valves separately

New types will not be protected against by regions infection or vaccination - leading new epidemics

Question 15

What is temporal diversity?

Answer 15

Mutation rate

So will be organised into clusters based on they’re ancestry in a specified assemblage over two or more time points

Question 16

What are the factors effecting resolution in sequencing dendrograms?

Answer 16

The high sequence mutation rate may not affect pathogenicity (antigenic drift)

Question 17

What is meant by the term a “constant molecular clock”?

Answer 17

Accurate predictions n molecular epidemiology thus requires an assumption that evolution is driven by a “constant molecular clock”

Question 18

What factors effect the speed of change “molecular clock”?

Answer 18

Bacteria replication rate - higher division rate provides higher mutation rate

DNA or RNA polymerase proof reading fidelity - some species have low fidelity promoting high mutation rate

Selection pressure from the host or environment - high selection pressure removes “weak” mutants - loss of selection pressure allows deletions

Degree of redundancy in the genome multiple copies of a single gene in the genome allow for mutations in on cop without compromising overall functionality

Transmission rate - high transmission rates relative to the mutation rate results in single strain outbreaks

Question 19

What genes change the most?

Answer 19

Hyper-variable genes change more rapidly than conserved genes

BUT conserved genes re more likely to be associated with phenotype and virulence

Question 20

What is convergent evolution?

Answer 20

Not all genetic changes are new, some may revert back to an older profile

Question 21

What happens when large rapid changes happen to the genome?

Answer 21

RARE

Often lead to escape from exiting herd protection

Question 22

What is epidemiological associations?

Answer 22

Transmission - hospital acquired infection

Reservoirs of infection - contact tracing determining introduction events

Spread or emergence of resistance