stuart: an R package for the curation of SNP genotypes from experimental crosses

Bourdon, Marie; Montagutelli, Xavier

doi:10.1093/g3journal/jkac219

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…Raw genotypes were curated using the stuart package [ 45 ]. QTL mapping was performed using R/qtl [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo

Bourdon,

Manet,

Conquet

et al. 2023

PLoS Pathog

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Zika virus (ZIKV) is a Flavivirus responsible for recent epidemics in Pacific Islands and in the Americas. In humans, the consequences of ZIKV infection range from asymptomatic infection to severe neurological disease such as Guillain-Barré syndrome or fetal neurodevelopmental defects, suggesting, among other factors, the influence of host genetic variants. We previously reported similar diverse outcomes of ZIKV infection in mice of the Collaborative Cross (CC), a collection of inbred strains with large genetic diversity. CC071/TauUnc (CC071) was the most susceptible CC strain with severe symptoms and lethality. Notably, CC071 has been recently reported to be also susceptible to other flaviviruses including dengue virus, Powassan virus, West Nile virus, and to Rift Valley fever virus. To identify the genetic origin of this broad susceptibility, we investigated ZIKV replication in mouse embryonic fibroblasts (MEFs) from CC071 and two resistant strains. CC071 showed uncontrolled ZIKV replication associated with delayed induction of type-I interferons (IFN-I). Genetic analysis identified a mutation in the Irf3 gene specific to the CC071 strain which prevents the protein phosphorylation required to activate interferon beta transcription. We demonstrated that this mutation induces the same defective IFN-I response and uncontrolled viral replication in MEFs as an Irf3 knock-out allele. By contrast, we also showed that Irf3 deficiency did not induce the high plasma viral load and clinical severity observed in CC071 mice and that susceptibility alleles at other genes, not associated with the IFN-I response, are required. Our results provide new insight into the in vitro and in vivo roles of Irf3, and into the genetic complexity of host responses to flaviviruses.

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“…Raw genotypes were curated using the stuart package [ 45 ]. QTL mapping was performed using R/qtl [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo

Bourdon,

Manet,

Conquet

et al. 2023

PLoS Pathog

Self Cite

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“…Raw genotypes were curated using the stuart package (43). QTL mapping was performed using R/qtl (44).…”

Section: Methodsmentioning

confidence: 99%

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced byIrf3deficiencyin vitrobut requires other variantsin vivo, not linked to the type I interferon response

Bourdon

Manet

Conquet

et al. 2023

Preprint

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Zika virus (ZIKV) is a Flavivirus responsible for recent epidemics in Pacific Islands and in the Americas. In humans, the consequences of ZIKV infection range from asymptomatic infection to severe neurological disease such as Guillain-Barré syndrome or fetal neurodevelopmental defects, suggesting the influence of host genetic factors. We previously reported similar diverse outcomes of ZIKV infection in mice of the Collaborative Cross, a collection of inbred strains with large genetic diversity. CC071 was the most susceptible strain with severe symptoms and lethality. Here, we investigated viral replication in mouse embryonic fibroblasts from CC071 and two resistant strains. CC071 showed enhanced viral replication associated with delayed induction of type-I interferons (IFN-I). Using a combination of genetic approaches, we identified a loss of function (LOF) mutation in theIrf3gene, specific to CC071, and demonstrated that it fully explains the defective IFN-I response and uncontrolled viral replication in CC071 MEFs. However, this mutation was not sufficient to induce the high plasma viral load and clinical severity observed in CC071 mice, indicating the involvement of other susceptibility genes in vivo. Considering the susceptibility of the CC071 strain to multiple viruses, our results provide new insight into the role of Irf3 in innate antiviral response.

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“…Genotyping arrays have been a staple in mouse research for more than two decades and have been successfully adopted for genetic QC and colony maintenance (Petkov et al 2004; Yang et al 2011; Morgan et al 2015; Andrews et al 2021; Amos-Landgraf et al 2022). Five years after its introduction, the MiniMUGA array has been used for genotyping over 40,000 mouse samples and the manuscript describing the array and its capabilities has been cited widely (Sigmon et al 2020; Birling et al 2022; Bourdon and Montagutelli 2022; Yoshiki et al 2022; Smith et al 2022). Part of MiniMUGA’s success is due to its unique characteristics, including discrimination between commercial substrains, robust chromosomal sex determination, and detection of commonly used constructs.…”

Section: Introductionmentioning

confidence: 99%

The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice

Blanchard,

Sigmon,

Brennan

et al. 2024

Preprint

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The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve array’s performance and the associated report’s usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA in 2020. Here we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for inbred strains and increase the number of constructs that can reliably be detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have made changes to the layout of the report, to simplify the interpretation and completeness of the analysis and added a table summarizing the ideogram. We believe that these changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

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stuart: an R package for the curation of SNP genotypes from experimental crosses

Cited by 6 publications

References 15 publications

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced byIrf3deficiencyin vitrobut requires other variantsin vivo, not linked to the type I interferon response

The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice

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