12. MOLECULAR EPIDEMIOLOGY OF DISEASE Flashcards
Define molecular epidemiology
- Epidemiology on a moelcular level, considers the genetic & environmental contributing factors
- The use of molecular methods as a resolved measure (diversity) of differences variables
What can molecular epidemiology help determine?
- Disease distribution (time & place)
- Disease transmission
- Disease manifestation
- Disease progression
What 3 factors does molecular epidemiology study?
- Transmission
- Resevoirs of infection (new or latent infection)
- Spread or emergence of resistance
What is molecular epidemiology useful for?
- Confirming outbreaks
- within institutions, community, past & in the lab - Identifying disease risks
- changes in virulence or resevoirs of infection
What functional characteristics of pathogens does molecular epidemiology study?
- Classical -> Biochemistry
- Serology -> O157 antigen
- Virulence -> Verotoxin
What genome characteristics of pathogens does molecular epidemiology consider?
- DNA/RNA
- Genes, AA sequence, base sequence, genome locus position -> Multiple possibilities
What type of test is used for functional diversity of pathogens?
- Single weighting tests
What are single weighting tests?
- Single weighting tests detect the presence or absence of a factor
- E.g toxin or antigen
What type of test is used for genomic diversity of pathogens?
- Multiple tests
- OR Additive weighting of single testing
What is additive weighting of tests?
- Multiple single tests are used which are all weighted differently
- Cannot use single tests to make a conclusion
- Combine multiple tests to confirm finding
Give an example of how additive weighting testing can be used
- Cell culture on sleective media for functional characteristics
- Serotyping with latex beads - antigen detection (e.g
- PCR of gene for toxin (e.g Veritoxin)
- Phage typing/testing
What are three categories of diversity in genomic characteristics?
- Factoral
- Functional
- Temporal
What is factoral genomic diversity?
- Presence or absence of a gene/base/change within the gene/genome relative to position in the genome
What is sploligotyping?
- Spoligotyping is arapid PCR based method which is used to genotype different strains of Mycobacterium Tuberclosis
What is a dendrogram?
- A dendrogram is a visual representation of clusters of data
- Cna show relatedness between clusters e.g strains of bacteria or pathogen
What is functional genomic diversity?
- Variation in the type of substitution
- Can be synonymous or non-synonymous
How can factoral tandem repeats be analysed?
- The number if tandem repeats can differ between pathogens
- Repeats are involved in control mechanisms for gene expression or DNA rearrangement
What is phylogenetic progression?
- Progressive single base substitutions in different positions of the sequence can lead to variants arising
- Phylogenetic progression refers to the relationship between different variants of pathogens
Why shoudn’t the same weight be given to all mutations?
- Simply identifying mutations doesn’t tell us much, we need to look at the AA change aswell to see whether the mutation was non-synonymous or synonymous
- Therefore, not all muttaions will result in variants
What is temporal genomic diversity?
- Mutation rate since last alteration
- average time for mutation to occur
What is antigenic drift?
- Antigen drift is the same antigen changing it’s sequence base by base
- GRADUAL alteration in sequence eventually leads to the antigen not being recognised by host immune system
- Arises from accumulation of mutations
What is antigenic shift?
- Antigenic shift refers to the emergence of a completely new sub-type/virus when two different strains of a virus combine or strains of different viruses combine
- Not gradual, SUDDEN replacement of antigen due to recombination with another viral sub-type
- Most commonly refers to influenza virus which has a H & N protein. E.g H2N2 & H3N3 may combine to form H2N3
- Formation of a completely new virus
- No immunity or vaccination protection
Why are some changes in viruses called variation not antigen shift or drift?
- E.g SARS-COV2 (COVID-19), changes arising are referred to as variants or variation because not enough evidence to say that these changes are definitely occuring in the antigens
- Therefore cannot conclude that these variants render the vaccine ineffective
What is the molecular clock?
- Molecular clock uses the calculated mutation rate to predate possible variants all the way back to the origin or emergence of a pathogen
- However, this is not always true and is based on assumptions
What two assumptions does the molecular clock make?
- Mutation rate is constant
2. Mutations are random
What 5 factors affect the speed of the molecular clock?
- Replication rate
- Proof redaing ability of DNA/RNA polymerase
- Redundancy in the genome - whether there is more than one copy of gene with the same function, allows for mutations to accumulate but there is still a functional copy of the gene
- Transmission of the virus
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How does replication rate affect the molecular clock?
- A higher division/replication rate means more opportunities for mutation
How does transmission affect the molecular clock?
- More transmission means more oportunities for mutation
- High transmission rate relative to the mutation rate results in single strain outbreaks and dissemination
Which genes are more susceptible to changes?
- Hyper-varaible genes change more than conserevd genes
- Conserved genes are less likely to undergo mutations, but any changes are associated with phenotype & virulence
What are the 4 steps in studying molecular epidemiology?
- Knowing the most appropriate variable
- Quantifying variations & deriving diversity
- Generating identities or clusters
- Analysisng data
- geographical location, prevalence, incidence, time of isolation, transmission ate, disaese severity
What is the difference between prevalence & incidence?
- Prevalence refers to the number of existing cases at a given point in time
- Incidence refers to the number of new cases developing within a given period of time
Define epidemiology
- Epidemiology is the branch of medical science that investigates all the factors that determine the presence or absence of diseases and disorders
