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

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Animal Models and Experimental Medicine 2024年第1期7卷 36-47页

作者： Roa'a H.S.Yosief Iqbal M.Lone Aharon Nachshon Heinz Himmelbauer irit gat-vik. Fuad A.Iraqi Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael School of Molecular Cell Biology and Biotechnology George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael Institute of Computational Biology Department of BiotechnologyUniversity of Natural Resources and Life SciencesMuthgasse 181190 ViennaAustria

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 *** 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 ***:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with *** tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was *** GENE-E analysis platform was used to generate a clustered heat map ***:Significant variation in body weight changes between CC lines was *** gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight ***,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 ***:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards *** a next step,eQTL analysis will be performed for our RNA-Seq *** 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

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Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice

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Animal Models and Experimental Medicine 2018年第3期1卷 212-220页

作者： Hanifa J.Abu-Toamih Atamni Maya Botzman Richard Mott irit gat-vik. Fuad A.Iraqi Sackler Faculty of Medicine Tel-Aviv University Faculty of Life Sciences Tel-Aviv University Department of Genetics University College of London

Background: Liver weight is a complex trait, controlled by polygenic factors and differs within populations. Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases ***: Liver weight of 506 mice generated from 39 different Collaborative Cross(CC) lines with both sexes at age 20 weeks old was determined using an electronic balance. Genomic DNA of the CC lines was genotyped with high-density single nucleotide polymorphic ***: Statistical analysis revealed a significant(P < 0.05) variation of liver weight between the CC lines, with broad sense heritability(H^2) of 0.32 and genetic coefficient of variation(CV_G) of 0.28. Subsequently, quantitative trait locus(QTL) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61-93.38 Mb(4.77 Mb). Three suggestive QTL were mapped at chromosomes 4, 12 and 13. The four QTL were designated as LWL1-LWL4 referring to liver weight loci 1-4 on chromosomes 8, 4, 12 and 13,***: To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice. Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.

关键词： candidate genes Collaborative Cross mouse model high genetic diverse mouse population liver weight quantitative trait locus mapping standard rodent diet

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