Infectious Diseases Genomics Flashcards
The red queen hypothesis
Species have to constantly evolve to stay alive when there’s competition against other species.
Host-pathogen arms race: antagonistic relationship leads to the necessity of pathogen to have the best virulent alleles to infect the organism and for the host to have the best resistant alleles to survive pathogenesis.
Law of constant extinction
Probability of extinction of a species is not dependent on how long it has already existed
Changes in genotype frequencies caused by
- Non random mating
- Mutation
- Migration
- Selection
- Drift (random fluctuations)
Selection for a certain allele can do what to the patterning of heritable parts of genome?
Selection that increases frequency of an allele can result in greater LD and a longer hallo type around the area being selected for.
What disrupts linkage disequilibrium?
Recombination hotspots..hence smaller haplotypes in older populations as more recombination happens
What is the average length of a human haplotype?
10kb
What is selective sweep and what’s an example of it?
Loss of all diversity at a specific locus.
Example would be either slc24a5 for skin pigmentation (and maybe disease resistance)…attributes for lightening of skin in Europeans.
What are trypanosomes?
Unicellular parasitic Protozoa.
They infect humans through tsetse fly bites.
Lethal disease = African sleeping sickness
What causes African sleeping sickness?
Trypanosoma brucei in Africa
What is GWAS and what does it stand for?
Genome-wide association study.
Collect DNA from cases and controls
Genotype everyone for tagSNPs
Test for associations of SNPs and the disease phenotype of disease status
What’s the arms race example with trypanosomes and humans?
We have a protein apoL1 that lyses trypanosomes. However trypanosomes developed an evolutionary adaptation to resist activity of apoL1 (subspecies= rhodesiense). Humans evolved to kill off new subspecies = alleles within apoL1: G1 and G2.
Those with G1 and G2 also associated in African Americans to cause late onset kidney disease
Can cure African sleeping sickness by giving them G1 and G2.
Why are the apoL1 variants part of natural selection?
Because even though they promote kidney disease, it prevents death before reproductive age. So after reproducing, get kidney disease. Doesn’t play a detrimental role in comparison to not having resistance to trypanosomes.
What do you look for in a GWAS study? What patterns?
Look for big haplotypes and the frequency of the haplotypes between diseased and non diseased. Also look for particular alleles with higher frequency in diseased vs non diseased. ApoL1 for example had two variants within the same region in mainly non diseased African Americans. This is an association of these mutations to the disease.
What was the point of and what did the GWAS in plasmodium find?
The point was to find variations in genomic make up in those resistant to antimalarial drugs vs non resistant.
They found that two alleles pfcrt and pfama-1 confer antimalarial drug resistance.
How was haplotype size analyzed in apoL1?
G1 and G2 had much bigger haplotype size than the normal avg of 10 kb. Bigger haplotypes for kidney disease is associated with these alleles within apoL1
