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bioRxiv · 10.1101/016873

The advent of genome-wide association studies for bacteria

Peter E Chen·B Jesse Shapiro
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Abstract

Highlights* The advent of the genome-wide association study (GWAS) approach provides a promising framework for dissecting the genetic basis of bacterial or archaeal phenotypes.\n\n* Bacterial genomes tend to be shaped by stronger positive selection, stronger linkage disequilibrium and stronger population stratification than humans, with implications for GWAS power and resolution.\n\n* An example GWAS in Mycobacterium tuberculosis genomes highlights the potentially confounding effects of linkage disequilibrium and population stratification.\n\n* A comparison of the traditional GWAS approach versus a somewhat orthogonal method based upon evolutionary convergence (phyC) shows strengths and weaknesses of both approaches.\n\nAbstractSignificant advances in sequencing technologies and genome-wide association studies (GWAS) have revealed substantial insight into the genetic architecture of human phenotypes. In recent years, the application of this approach in bacteria has begun to reveal the genetic basis of bacterial host preference, antibiotic resistance, and virulence. Here, we consider relevant differences between bacterial and human genome dynamics, apply GWAS to a global sample of Mycobacterium tuberculosis genomes to highlight the impacts of linkage disequilibrium, population stratification, and natural selection, and finally compare the traditional GWAS against phyC, a contrasting method of mapping genotype to phenotype based upon evolutionary convergence. We discuss strengths and weaknesses of both methods, and make suggestions for factors to be considered in future bacterial GWAS.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC=\"FIGDIR/small/016873_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@431609org.highwire.dtl.DTLVardef@5bad1borg.highwire.dtl.DTLVardef@c1ff30org.highwire.dtl.DTLVardef@58e539_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Peter E Chen, B Jesse Shapiro. 2015-03-22. The advent of genome-wide association studies for bacteria. https://doi.org/10.1101/016873

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