Understanding the genetic basis of susceptibility and severity of infectious diseases Flashcards
Why do we undertake genetic studies of infectious diseases?
Identify fundamental pathways causing susceptibility
Identify those susceptible
Identify key components of pathophysiology
Explain individual differences in clinical presentation or outcome
Identify targets for therapy
What is HapMap?
Program to chart genetic variation within the human genome- an international effort to construct a map of the patterns of SNOs (single nucleotide and other variants in genome) that occur across populations in Africa, Asia and United states
What advances in technology for genome sequencing have there been?
High throughput sequencing
SNP microarrays of 500,000 to 1 million SNPs
RNA expression arrays
Bioinformatic methods for large data set
Extensive databases on genes and function
How common is infection with mycobacterial TB?
Very common- 60% of population of Africa may be infected by mycobacterial TB
Why do only a small percentage of those infected with mycobacterial TB go on to develop disease?
The outcome is affected by bacterial, environmental and genetic factors which lead to either a successful immune response or disease- unsuccessful immune response
What is the concept of homozygosity by descent?
If a rare recessive defect is introduced into a population by a common ancestor, the affected patients will be homozygous not only for the abnormal gene but also for genes in the vicinity of the defect (occurs with inbreeding)
How can you identify the chromosomal location of abnormal genes in homozygosity by descent?
Searching for regions of the genome for which all the affected individuals are homozygous by descent
What is the IFN-gamma receptor and which cells express it?
It is expressed on all cells. It is a type II cytokine receptor coded for by a gene on chromosome 6
What are all mutations of IFN gamma associated with?
Susceptibility to mycobacteria and salmonella
What forms of meningococcal disease are there vaccines for?
A and C
How does infection with meningococcal disease come about?
It comes on very rapidly spreading from the nose into the bloodstream then other organs and the brain
Why is meningococcal disease remarkable?
It is so variable- it can lead to asymptomatic bacteraemia, meningitis, septic shock or purpura fulminans
What susceptibility genes are there?
Control colonisation and invasion and survival in blood
More present in cases vs controls
What do severity genes do?
They determine the inflammatory response, extent of coagulopathy and organ failure
Same frequency in case vs controls
What causes recurrent meningococcal disease?
Complement deficiency
