host genetics and infectious disease Flashcards
how is blood group associated with malaria vivax?
malaria vivax can only infect duffy positive patients
these are patients with DARC expressed on their surface
what are some genes associated with malaria that affect the RBC?
genes associated with the structure of RBC:
- alpha globulin
- beta globuln
- erythrocyte band 3
- glycophorin A
- glycophorin B
what gene mutation do people who are immune to HIV have?
- homozygous for 32 bp deletion in the CCR5 gene
- Frameshift mutation and premature stop codon
- Protein is not expressed at cell surface
- CCR5 is a co-receptor for HIV
what happens to your tuberculin test if you have a poor immune response to primary TB infection?
it will be negative
what are evolutionary considerations for host genetics an infectious disease?
- infectious diseases are a force for human evolution
- host defence genes are more diverse than other genes
- human immune response genes are more polymorphic than any other species
how are host genes seen to be related to infectious disease?
- many can be exposed to an infection but only a few will develop the disease
- there is familial clustering of genetic diseases
- there is interpolation difference in the prevalence of infectious diseases
- adoption studies show that adoptees are 5.8 times more at risk of ID if their parents died from it
- there is high concordance in ID among monozygotic twins compared to dizygotic
why do we identify genes that predispose/protect from disease?
- to understand disease pathogenesis
- to identify the pathways important for immunity when designing therapies against ID
what are the different ways we can identify human ID susceptibility genes?
- animal models
- mendelian disease in humans
- analysys through gene sequencing
- family linkage studies vs population based association studies
- quantative trait analysis
what type of polymorphism is sickle cell?
b-globulin
which binding site is mutated in Duffy negative individuals?
- GATA1
- the transcription factor GATA-1 activates DARC gene
why do duffy individuals express DARC on heir leucocytes?
because GATA1 binding is only required for expression of DARC on erythrocytes
DARC can still be expressed on leukocytes without GATA1 binding
how does maraviroc work against HIV?
blocks the CCR5 receptor for HIV
why is TB a complex trait?
infection is influenced by…
- pathogen
- host immune response
- environment
what are some mutations in immune response molecules associated with malaria?
HLA-B HLA-DRB1 TNF iNOS ABO blood group ICAM-1
what are some groups of people that are at risk of TB?
- Extremes of age
- co infection with HIV
- post measles
- diabetes
- renal disease
- steroid therapy
- anti-TNF treatment
