L4: Molecular Markers II and III Flashcards
Definition
What is a cluster?
Cases linked by the same transmission chain (same outbreak)
We have identified a cluster. Can we say that the cases in the cluster transmitted to one another?
No. Cluster analysis does not give any information about transmission. The cases in question could all have been transmitted from a source outside the cluster and not all of them have to be infected by the same source.
In an outbreak variant A was much more common than variant B. Variant A is thus more transmissible, correct?
Not necessarily. Variant B could be an imported case and could be highly transmissible in region B and this could just not yet be observed in region A. Also, we must always keep in mind that we could have sampling bias!
Decide if this statement is correct:
You always need more markers for strain resolution than for species resolution.
This is not true. You can have just one marker that is fast evolving, while you may need several slowly evolving genes for species resolution.
Why is it difficult to do whole genome sequencing in organisms that have many repetitive streches?
Because of the nature of WGS (=assembly of short contigs) one does not know how to asseble these repetitive and overlapping streches. This is why they are often discarded (along with mobile elements).
How does comparative genomics based on WGS work?
There are two major things commonly done with WGS data:
1. Cluster analysis
2. Phylogenetics
Multiple sequence alignment lets you “map” mutations onto a phylogenetic tree.
Does the branch length in a phylogenetic tree have any info/meaning?
Yes. Generally branch length represents genetic distance, a scale bar is needed to calculate gen. distance.
Visually on a phylogenetic tree, what is an inidcation for an outbreak?
A section that has many species/strains with very short genetic distance i.e. almost no horizontal branches.
Definition
What is topology?
Topology refers to the position of the branches in a tree relative to one another. It does not take into account branch length.
How do you calculate genetic distance from a tree?
You sum up the horizontal branch length from one species to the other.
Definition
What is homoplasy?
Homoplasy refers to the phenomenon when the same mutation is appearing multiple times independently. This indicates a strong selective pressure. This pattern can be seen in e.g. acquired drug resistance.
You observe several drug resistant phenotypes in a phylogenetic tree. How can you tell if this is acquired or primary resistance (by transmission)?
If the mutation occurs in several species not linked by common ancestor -> homoplasy/acquired resistance.
If the mutation is present in virtually all descendants of one ancestor-> primary resistance.
How can you date trees?
For this, you need information about the molecular clock of the gene in question. If you take this into account mathematically you can get from genetic distance to time.
Phylogenies do NOT represent transmission events. But what does?
You can get from phylogenies to transmission trees. For this dating is needed as well as complex mathematical modelling that takes things like pathogen transmission, sampling and evolution into account.
