The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform

Yahya Sohrabi - One of the best experts on this subject based on the ideXlab platform.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus.
    BMC neuroscience, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus
    BMC, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Abstract Background Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. Methods To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Results Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. Conclusions The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2016
    Co-Authors: Yahya Sohrabi, Tetyana Kobets, Valeriya Volkova, Igor Grekov, Iryna Kurey, Peter Demant
    Abstract:

    Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5 % genes from the resistant parental Strain STS/A and 87.5 % genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology. Methods: We analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c6CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses. Principal Findings: We mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loc

  • Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
    PLoS neglected tropical diseases, 2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    Background L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    BackgroundL. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.MethodsWe analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.Principal FindingsWe mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.ConclusionWe present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.

Valeriya Volkova - One of the best experts on this subject based on the ideXlab platform.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus.
    BMC neuroscience, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus
    BMC, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Abstract Background Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. Methods To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Results Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. Conclusions The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2016
    Co-Authors: Yahya Sohrabi, Tetyana Kobets, Valeriya Volkova, Igor Grekov, Iryna Kurey, Peter Demant
    Abstract:

    Background: L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5 % genes from the resistant parental Strain STS/A and 87.5 % genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology. Methods: We analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c6CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses. Principal Findings: We mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loc

  • Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
    PLoS neglected tropical diseases, 2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    Background L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    BackgroundL. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.MethodsWe analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.Principal FindingsWe mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.ConclusionWe present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.

Matyáš Šíma - One of the best experts on this subject based on the ideXlab platform.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus.
    BMC neuroscience, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus
    BMC, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Abstract Background Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. Methods To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Results Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. Conclusions The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans

  • Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
    PLoS neglected tropical diseases, 2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    Background L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    BackgroundL. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.MethodsWe analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.Principal FindingsWe mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.ConclusionWe present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.

Jarmila Vojtíšková - One of the best experts on this subject based on the ideXlab platform.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus.
    BMC neuroscience, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus
    BMC, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Abstract Background Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. Methods To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Results Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. Conclusions The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans

  • Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
    PLoS neglected tropical diseases, 2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    Background L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.

  • Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
    2013
    Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena Svobodová
    Abstract:

    BackgroundL. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the Recombinant Congenic Strain CcS-16 carrying 12.5% genes from the resistant parental Strain STS/A and 87.5% genes from the susceptible Strain BALB/c is more susceptible to L. tropica than BALB/c. We used these Strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.MethodsWe analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 Strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.Principal FindingsWe mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.ConclusionWe present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.

Lucie Mrázková - One of the best experts on this subject based on the ideXlab platform.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus.
    BMC neuroscience, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

  • A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus
    BMC, 2018
    Co-Authors: Martin Palus, Yahya Sohrabi, Matyáš Šíma, Valeriya Volkova, Jarmila Vojtíšková, Karl W. Broman, Hynek Strnad, Daniel Růžek, Martina Slapničková, Lucie Mrázková
    Abstract:

    Abstract Background Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the Recombinant Congenic Strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the Strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two Strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. Methods To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. Results Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes’ functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS Strain. Conclusions The robust genetic system of Recombinant Congenic Strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans