Genetic resistance and susceptibility to infectious disease Flashcards
examples of 2 blood groups which limit pathogen entry
duffy negative, dantu
duffy negative blood group- what does it protect against, what is the mutation
creates both regular and symptomatic protection from plasmodium vivax
single polymorphism at the duffy antigen receptor on RBCs
dantu blood group- what is it, what are the benefits
mutation in glycophorin
associated with protection from early stage plasmodium infection
potential mechanism for dantu blood type altering infection susceptibility
increasing tension on blood cells, more failed invasions?
other blood cell mutations which could be involved in disease susceptibility
CCR5-∆32 mutation on chemokine receptors- homozygotes seem to be resistant to HIV - however does not seem to have originated as a HIV thing
non-secretor mutations- no expression of ABO antigens in body fluids, prevents infection w norovirus?? bc virus needs to bind to these antigens in body fluids
2 examples of mutations which limit infection impact
haemoglobinopathies- e.g. sickle cell trait- bad when homozygous but protective against severe infections like malaria
southeast asian ovalocytosis- oval shaped RBCs eading to resistance to malaria, but lethal homozygosity
how does sickle cell trait limit malaria infection severity?
-enhanced phagocytosis of infected ells- seen in the lab
-altered cell structure, prevention of cytoadhesion so infection spreads less?
example of MHC diversity association with infection
HLA-B53 (HLA = MHC)- protects against malaria, as can present a specific plasmodium peptide
associations w HIV- can identify specific amino acids which seem to be able to predict viral load- related to which peptides the HLA expresses and how easy it is for the virus to vary it
associations w avian flu also- moreso because chickens have a limited repertoire of MHC loci
matching allele model
way of mapping parasite fitness against the alleles it infects- exact match is required for infection, goes along with ideas of negative frequency-dependent selection
gene for gene model
expect a broad host range from one pathogen genotype- more about being the ‘best’ pathogen or host- sort of the opposite end of a continuum with MA models
matching alleles- real world example
daphnia and pathogens seem to ‘swap’ fitnesses, when you analyse alleles- dynamicism which maintains polymorphism
gene for gene- real example
norovirus evolution- seems very adaptable, and so is the host in terms of the secretor-non-secretor thing- not just 1 strain > 1 host type
two outcomes of pathogen response to the development of immunity
-pathogen adopts a strain structure, and hosts with bad immunity just die
-pathogens cycle between combinations of non-overlapping strains, driving MHC types to be more or less advantageous
2 ways of identifying infection associated host loci
case control studies- how do people who respond differently to infection differ genetically? can get odds ratios etc for associations between genetic features and disease outcome
GWAS- more bioinformatics approach, library of SNPs and look at what is associated w the disease
