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

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

article

Ailene MacPherson¹  Sarah P. Otto¹  Scott L. Nuismer³ 

[1] Department of Zoology,University of British Columbia, Vancouver, V6T 1Z4, Canada;Biodiversity Research Centre, University of British Columbia, Vancouver, V6T 1Z4, Canada;Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844

关键词: host–parasite coevolution;    GWAS;    Daphnia magna;    Pastueria ramosa;    genetic architecture of resistance;   

DOI  :  10.1534/genetics.117.300481

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

CC BY