"Select and Resequence" Methods Enable a Genome-Wide Association Study of the Dimorphic Human Fungal Pathogen...

Area of Science:

• Microbiology
• Genetics
• Mycology

Background:

• Next-generation sequencing provides extensive genotype data for wild populations.
• Interpreting genotype-phenotype links is challenging, especially in nonmodel organisms.
• Coccidioides posadasii is a thermally dimorphic pathogenic fungus relevant to human health.

Purpose of the Study:

• To pioneer a method for mapping genotype to phenotype in natural populations.
• To identify genetic loci associated with temperature-dependent growth in Coccidioides posadasii.
• To demonstrate the utility of pooled strain phenotyping and association mapping for nonmodel systems.

Main Methods:

• Sequencing genomes of 66 natural Coccidioides posadasii isolates.
• Pooling strains and competing them in growth assays at different temperatures (37°C and room temperature).
• Inferring strain abundance from DNA sequencing coverage and performing genome-wide association tests.

Main Results:

• Identified genetic loci predictive of temperature-dependent growth.
• Top hits included variants in gene D8B26_001557, part of the Ryp1 regulatory network.
• Demonstrated successful genotype-phenotype mapping in a nonmodel fungal system.

Conclusions:

• Pooled strain phenotyping and association mapping are powerful tools for genetic dissection.
• This method facilitates the study of trait variation in organisms that are difficult to manipulate.
• The findings provide insights into the genetic basis of thermal dimorphism in Coccidioides posadasii.