Infection 1: Host genetics and infectious disease

Question 1

Evolutionary considerations of infectious disease

Answer 1

Infectious diseases are a major selective force in human evolution

Host defense genes are more diverse than any other genes

Human immune response genes more polymorphic than any other species

Question 2

Clinical considerations of infectious disease

Answer 2

Many exposed to infection; few develop disease

Familial clustering of infectious disease

Inter-population differences in prevalence

Adoption studies: 5.8 x increased risk for adoptees with a biological parent who died from infectious disease

Question 3

Identifying human infectious susceptibility genes

Answer 3

Animal models

Mendelian disease in humans

Analysis of infectious disease as complex traits

Quantitative trait analysis

Question 4

HIV infection

Answer 4

Some individuals remain uninfected b yHIV despite repeated exposure

Others become HIV+ but disease does not develop

Human CD4 transgenic mice could not be infected with HIV despite carrying this known receptor for HIV

Resistant individuals found to be 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

Question 5

Outcome of mycobacterial infection

Answer 5

90%

• good immune response
• tuberculin positive
• well

10%

• poor immune response
• tuberculin negative
• disease