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 candidat...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.展开更多
Wild rice O.officinalis(CNW 258,CNW 259)andO.eichingeri(CNW 260,CNW 261)have CCgenome and high resistance to brown planthopper(BPH)and whitebacked planthopper(WBPH).Totransfer the resistant gene(s)of the wild rice int...Wild rice O.officinalis(CNW 258,CNW 259)andO.eichingeri(CNW 260,CNW 261)have CCgenome and high resistance to brown planthopper(BPH)and whitebacked planthopper(WBPH).Totransfer the resistant gene(s)of the wild rice intoAsian cultivated rice,the interspecific crosses be-tween O.sativa L.(AA)and O.officinalis and O.展开更多
Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically ...Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.展开更多
The Collaborative Cross(CC)mouse model is a next‐generation mouse genetic reference population(GRP)designated for a high‐resolution quantitative trait loci(QTL)mapping of complex traits during health and disease.The...The Collaborative Cross(CC)mouse model is a next‐generation mouse genetic reference population(GRP)designated for a high‐resolution quantitative trait loci(QTL)mapping of complex traits during health and disease.The CC lines were generated from reciprocal crosses of eight divergent mouse founder strains composed of five classical and three wild‐derived strains.Complex traits are defined to be controlled by variations within multiple genes and the gene/environment interactions.In this article,we introduce and present variety of protocols and results of studying the host response to infectious and chronic diseases,including type 2 diabetes and metabolic diseases,body composition,immune response,colorectal cancer,susceptibility to Aspergillus fumigatus,Klebsiella pneumoniae,Pseudomonas aeruginosa,sepsis,and mixed infections of Porphyromonas gingivalis and Fusobacterium nucleatum,which were conducted at our laboratory using the CC mouse population.These traits are observed at multiple levels of the body systems,including metabolism,body weight,immune profile,susceptibility or resistance to the development and progress of infectious or chronic diseases.Herein,we present full protocols and step‐by‐step methods,implemented in our laboratory for the phenotypic and genotypic characterization of the different CC lines,mapping the gene underlying the host response to these infections and chronic diseases.The CC mouse model is a unique and powerful GRP for dissecting the host genetic architectures underlying complex traits,including chronic and infectious diseases.展开更多
基金European Sequencing and Genotyping Institutes(ESGI),Grant/Award Number:075491/Z/04,085906/Z/08/Z and 090532/Z/09/ZTel-Aviv University(TAU)。
文摘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.
文摘Wild rice O.officinalis(CNW 258,CNW 259)andO.eichingeri(CNW 260,CNW 261)have CCgenome and high resistance to brown planthopper(BPH)and whitebacked planthopper(WBPH).Totransfer the resistant gene(s)of the wild rice intoAsian cultivated rice,the interspecific crosses be-tween O.sativa L.(AA)and O.officinalis and O.
基金Israeli Science Foundation (ISF),Grant/Award Number 1085/18German Israeli Science Foundation (GIF),Grant/Award Number I-63-410.20-2017+1 种基金Binational Science Foundation (BSF),Grant/Award Number 2015077Tel-Aviv University
文摘Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.
基金Hendrech and Eiran Gotwert FundWellcome, Grant/Award Number: 085906/Z/08/Z, 075491/Z/04 and 090532/Z/09/Z+6 种基金Tel-Aviv UniversityIsraeli Science foundation, Grant/Award Number: 429/09, 961/15 and 1085/18Binational Science Foundation, Grant/Award Number: 2015077German Israeli Science Foundation, Grant/Award Number: I-63-410.20-2017Israeli Cancer Research FundCancer Research Counsel-UK Cancer Biology Research Center
文摘The Collaborative Cross(CC)mouse model is a next‐generation mouse genetic reference population(GRP)designated for a high‐resolution quantitative trait loci(QTL)mapping of complex traits during health and disease.The CC lines were generated from reciprocal crosses of eight divergent mouse founder strains composed of five classical and three wild‐derived strains.Complex traits are defined to be controlled by variations within multiple genes and the gene/environment interactions.In this article,we introduce and present variety of protocols and results of studying the host response to infectious and chronic diseases,including type 2 diabetes and metabolic diseases,body composition,immune response,colorectal cancer,susceptibility to Aspergillus fumigatus,Klebsiella pneumoniae,Pseudomonas aeruginosa,sepsis,and mixed infections of Porphyromonas gingivalis and Fusobacterium nucleatum,which were conducted at our laboratory using the CC mouse population.These traits are observed at multiple levels of the body systems,including metabolism,body weight,immune profile,susceptibility or resistance to the development and progress of infectious or chronic diseases.Herein,we present full protocols and step‐by‐step methods,implemented in our laboratory for the phenotypic and genotypic characterization of the different CC lines,mapping the gene underlying the host response to these infections and chronic diseases.The CC mouse model is a unique and powerful GRP for dissecting the host genetic architectures underlying complex traits,including chronic and infectious diseases.
