Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach  

作　　者：Roa'a H.S.Yosief Iqbal M.Lone Aharon Nachshon Heinz Himmelbauer Irit Gat-Viks Fuad A.Iraqi 

机构地区：[1]Department of Clinical Microbiology and Immunology,Sackler Faculty of Medicine,Tel-Aviv University,Tel-Aviv,Israel [2]School of Molecular Cell Biology and Biotechnology,George S.Wise Faculty of Life Sciences,Tel Aviv University,Tel Aviv,Israel [3]Institute of Computational Biology,Department of Biotechnology,University of Natural Resources and Life Sciences,Muthgasse 18,1190 Vienna,Austria

出　　处：《Animal Models and Experimental Medicine》2024年第1期36-47,共12页动物模型与实验医学（英文）

基　　金：European Sequencing and Genotyping Institutes(ESGI),Grant/Award Number:075491/Z/04,085906/Z/08/Z and 090532/Z/09/Z;Tel-Aviv University(TAU)。

摘　　要：Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.

关 键 词：aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-SEQ 

分 类 号：R-33[医药卫生]