IDENTFYING GENETIC SUSCEPTIBILITY TO FUNGAL INFECTION USING COLLABORATIVE CROSS MICE AND HEPATIC GENE EXPRESSION AND RNAseq APPROACH

Introduction: Aspergillus fumigatus (AF), one of the most ubiquitous fungus, which infection potency suggested to be strongly controlled by the host genetic background. Results of our previous publication, when used Collaborative Cross (CC) mouse model, reported Quantitative Trait Loci (QTL), that mapped on chromosomes 2, 3, 8, 10, 15 and 18, associated with the host susceptibility to AF.

Aims: Searching for candidate genes associated with host susceptibility towards Aspergillus fumigates (AF) using CC lines and hepatic gene expression approach.

Materials and Methods: 31 male mice of 25 CC lines at age of eight weeks old were infected with AF. Body Weight (BW) change was monitored for five days of the challenge. Liver tissues were extracted from these mice at five days post infection and next generation RNA-sequencing was analyzed. GENE-E analysis platform was used to generate clustered heat map matrix.

Results and Conclusions: Significant variation between CC lines was observed for BW (p-0.05) Hepatic gene expression revealed twelve top prioritized candidate genes differentially expressed in resistant versus susceptible mice. Interestingly, three genes are located within genomic intervals implicated by mapped QTL; Gm16270 and Stox1 on chromosome 10, and Gm11033 on chromosome 8. Our findings emphasize the power of CC mouse model in fine mapping of the strong genetic components underlying susceptibility towards AF.