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Keeping Pace with the Red Queen: Identifying the Genetic Basis of Susceptibility to Infectious Disease.

ABSTRACT: Genome-wide association studies are widely used to identify "disease genes" conferring resistance/susceptibility to infectious diseases. Using a combination of mathematical models and simulations, we demonstrate that genetic interactions between hosts and parasites [genotype-by-genotype (G × G) interactions] can drastically affect the results of these association scans and hamper our ability to detect genetic variation in susceptibility. When hosts and parasites coevolve, these G × G interactions often make genome-wide association studies unrepeatable over time or across host populations. Reanalyzing previously published data on Daphnia magna susceptibility to infection by Pasteuria ramosa, we identify genomic regions consistent with G × G interactions. We conclude by outlining possible avenues for designing more powerful and more repeatable association studies.

SUBMITTER: MacPherson A

PROVIDER: S-EPMC5788537 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Keeping Pace with the Red Queen: Identifying the Genetic Basis of Susceptibility to Infectious Disease.

MacPherson Ailene A Otto Sarah P SP Nuismer Scott L SL

Genetics 20171209 2

Genome-wide association studies are widely used to identify "disease genes" conferring resistance/susceptibility to infectious diseases. Using a combination of mathematical models and simulations, we demonstrate that genetic interactions between hosts and parasites [genotype-by-genotype (G × G) interactions] can drastically affect the results of these association scans and hamper our ability to detect genetic variation in susceptibility. When hosts and parasites coevolve, these G × G interaction ...[more]

PMID: 29223971

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