Association Studies

Many studies have identified genetic variants that are implicated in important pathogen phenotypes–such as virulence–in a laboratory setting. Likewise much work has been done identifying variants in the human population that affect susceptibility to disease. What is still unclear, however, is whether variants affecting the disease phenotype can be identified in “natural” pathogen populations.

One way to investigate the relationship between genotype and phenotype is to see which variants are associated with a particular phenotype in panels of cases and controls. We are seeking to carry out whole-genome association studies to try and pin down genetic variants associated with phenotypes such as increased virulence or mortality in various study species.

Using whole-genome sequencing data for panels of case and control isolates, we genotype each isolate and for each variant site, ask whether the variant is distributed at random among cases and controls, or associated with one or the other group. We can also ask whether any variants we discover have arisen independently in multiple clades, a scenario which would give weight to the hypothesis that they provide an adaptive advantage to the organism, or are signatures of ancient population structure between lineages.