Host genetics and infectious disease Flashcards
Infections that show genetic susceptibility in twin studies
Helicobacter pylori (81% in DZ twins)
Importance of identifying genes that predispose to/ protect from disease
Helps to better under the pathogenesis of certain diseases.
Allows development of new treatments and vaccines.
Methods of identifying human infectious disease susceptibility genes.
Animal models
Mandelian disease
Analysis of IDs as complex traits
- Family based vs population based studies
Quantitative trait analysis.
GATA-1 and malaria resistance
GATA-1 is a transcription factor necessary for the activation of DARC.
DARC is present on erythrocytes and leucocytes.
F. vivax malaria needs to bind to DARC in order to infect RBC.
Mutation of GATA-1 (Duffy negative), preventing activation of DARC= resistance to f. vivax malaria.
Genes associated with malaria
HLA-B
alpha and beta globing
G6P DH
Spectrin
Glycophorin A and B
Duffy chemokine receptor
DARC and malaria
Duffy antigen/ chemokine receptor is a receptor present on erythrocytes and leucocytes.
Being ‘duffy negative’= not having the DARC.
- Protective against f. vivax and knowlesi malaria.
Receptor is encoded on chromosome 1.
Genetic resistance in HIV
32 bp deletion in CCR5 gene
- Causes non-sense mutation via frameshift mutation
- CCR5 is a receptor on plasma surface necessary for HIV entry into cell?
- Homozygous for this shows resistance
Genetic predisposition to developing mycobacteria infections
400 highly polymorphic micro satellite markers across all chromosomes
Premature stop codon on IFNGR1
- Increased susceptibility
IFNGR1 and mycobacterium infections
IFNGR1 codes for IFN-G receptor present on macrophages.
Carrier of recessive mutation in this gene causing premature stop codon prevents intracellularly signalling.
- Macrophage unable to respond to IFN-g signalling from T cell.
- Macrophage cannot be activated to handle mycobacteria infection.
Mutation in five genes of IL-12/ IFN-G causes mandolin disease
