Genetic Basis of Susceptibility

Question 1

What are the main sites for generic influence in susceptibility genes and in severity genes? Which of these genes has a greater frequency in cases vs controls?

Answer 1

Susceptibility genes:
Control colonisation, invasion of bloodstream and survival in blood.

Severity genes:
Control inflammatory response, extent of coagulopathy, and organ failure.

Susceptibility genes have greater frequency in cases, but severity genes only in severe cases

Question 2

How can genetics studies be useful in infectious disease?

Answer 2

Help identify pathophysiology and targets for therapy and susceptible populations, and help explain differences in severity

Question 3

What gene is associated with familial atypical mycobacteria infection and disseminated BCG?

Answer 3

The IFN-y Receptor gene on chromosome 6. A single base deletion at position 130 and frame shift leads to a premature stop codon

Question 4

How does meningococcal protein (FhbP) make N. meningiditis a ‘smart’ pathogen?

Answer 4

Binds Complement factor H, inhibiting C3b also there is reduced killing

Question 5

What does CARMA1/Card 11 defect result in?

Answer 5

Inability to produce IL2 to CD3/CD28 stimulation and inability to activate NFKB.