12. MOLECULAR EPIDEMIOLOGY OF DISEASE Flashcards

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1
Q

Define molecular epidemiology

A
  • Epidemiology on a moelcular level, considers the genetic & environmental contributing factors
  • The use of molecular methods as a resolved measure (diversity) of differences variables
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2
Q

What can molecular epidemiology help determine?

A
  • Disease distribution (time & place)
  • Disease transmission
  • Disease manifestation
  • Disease progression
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3
Q

What 3 factors does molecular epidemiology study?

A
  1. Transmission
  2. Resevoirs of infection (new or latent infection)
  3. Spread or emergence of resistance
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4
Q

What is molecular epidemiology useful for?

A
  1. Confirming outbreaks
    - within institutions, community, past & in the lab
  2. Identifying disease risks
    - changes in virulence or resevoirs of infection
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5
Q

What functional characteristics of pathogens does molecular epidemiology study?

A
  1. Classical -> Biochemistry
  2. Serology -> O157 antigen
  3. Virulence -> Verotoxin
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6
Q

What genome characteristics of pathogens does molecular epidemiology consider?

A
  • DNA/RNA

- Genes, AA sequence, base sequence, genome locus position -> Multiple possibilities

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7
Q

What type of test is used for functional diversity of pathogens?

A
  • Single weighting tests
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8
Q

What are single weighting tests?

A
  • Single weighting tests detect the presence or absence of a factor
  • E.g toxin or antigen
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9
Q

What type of test is used for genomic diversity of pathogens?

A
  • Multiple tests

- OR Additive weighting of single testing

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10
Q

What is additive weighting of tests?

A
  • Multiple single tests are used which are all weighted differently
  • Cannot use single tests to make a conclusion
  • Combine multiple tests to confirm finding
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11
Q

Give an example of how additive weighting testing can be used

A
  1. Cell culture on sleective media for functional characteristics
  2. Serotyping with latex beads - antigen detection (e.g
  3. PCR of gene for toxin (e.g Veritoxin)
  4. Phage typing/testing
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12
Q

What are three categories of diversity in genomic characteristics?

A
  1. Factoral
  2. Functional
  3. Temporal
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13
Q

What is factoral genomic diversity?

A
  • Presence or absence of a gene/base/change within the gene/genome relative to position in the genome
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14
Q

What is sploligotyping?

A
  • Spoligotyping is arapid PCR based method which is used to genotype different strains of Mycobacterium Tuberclosis
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15
Q

What is a dendrogram?

A
  • A dendrogram is a visual representation of clusters of data
  • Cna show relatedness between clusters e.g strains of bacteria or pathogen
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16
Q

What is functional genomic diversity?

A
  • Variation in the type of substitution

- Can be synonymous or non-synonymous

17
Q

How can factoral tandem repeats be analysed?

A
  • The number if tandem repeats can differ between pathogens

- Repeats are involved in control mechanisms for gene expression or DNA rearrangement

18
Q

What is phylogenetic progression?

A
  • 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
19
Q

Why shoudn’t the same weight be given to all mutations?

A
  • 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
20
Q

What is temporal genomic diversity?

A
  • Mutation rate since last alteration

- average time for mutation to occur

21
Q

What is antigenic drift?

A
  • 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
22
Q

What is antigenic shift?

A
  • 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
23
Q

Why are some changes in viruses called variation not antigen shift or drift?

A
  • 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
24
Q

What is the molecular clock?

A
  • 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
25
Q

What two assumptions does the molecular clock make?

A
  1. Mutation rate is constant

2. Mutations are random

26
Q

What 5 factors affect the speed of the molecular clock?

A
  1. Replication rate
  2. Proof redaing ability of DNA/RNA polymerase
  3. 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
  4. Transmission of the virus
    .
27
Q

How does replication rate affect the molecular clock?

A
  • A higher division/replication rate means more opportunities for mutation
28
Q

How does transmission affect the molecular clock?

A
  • More transmission means more oportunities for mutation

- High transmission rate relative to the mutation rate results in single strain outbreaks and dissemination

29
Q

Which genes are more susceptible to changes?

A
  • Hyper-varaible genes change more than conserevd genes

- Conserved genes are less likely to undergo mutations, but any changes are associated with phenotype & virulence

30
Q

What are the 4 steps in studying molecular epidemiology?

A
  1. Knowing the most appropriate variable
  2. Quantifying variations & deriving diversity
  3. Generating identities or clusters
  4. Analysisng data
    - geographical location, prevalence, incidence, time of isolation, transmission ate, disaese severity
31
Q

What is the difference between prevalence & incidence?

A
  • 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
32
Q

Define epidemiology

A
  • Epidemiology is the branch of medical science that investigates all the factors that determine the presence or absence of diseases and disorders