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Angabin Matin - One of the best experts on this subject based on the ideXlab platform.
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Testicular germ cell tumor susceptibility genes from the consomic 129.MOLF-Chr19 mouse Strain
Mammalian Genome, 2007Co-Authors: Rui Zhu, Lianchun Xiao, Angabin MatinAbstract:Chromosome Substitution Strains (CSS or consomic Strains) are useful for mapping phenotypes to Chromosomes. However, huge efforts are needed to identify the gene(s) responsible for the phenotype in the complex context of the Chromosome. Here we report the identification of candidate disease genes from a CSS by using a combination of genetic and genomic approaches and by using knowledge about the germ cell tumor disease etiology. We used the CSS 129.MOLF-Chr19 Chromosome Substitution Strain, in which males develop germ cell tumors of the testes at an extremely high rate. We were able to identify three protein-coding genes and one microRNA on Chromosome 19 that have previously not been implicated to be testicular tumor susceptibility genes. Our findings suggest that changes in gene expression levels in the gonadal tissues of multiple genes from Chr 19 likely contribute to the high testicular germ cell tumor (TGCT) incidence of the 129.MOLF-Chr19 Strain. Our data advance the use of CSS to identify disease susceptibility genes and demonstrate that the 129.MOLF-Chr19 Strain serves as a useful model to elucidate the genetics and biology of germ cell transformation and tumor development.
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Testicular cancer susceptibility in the 129.MOLF-Chr19 mouse Strain: additive effects, gene interactions and epigenetic modifications
Human Molecular Genetics, 2003Co-Authors: Kirsten K. Youngren, Joseph H. Nadeau, Angabin MatinAbstract:Testicular germ cell tumors (TGCTs) are the most common solid cancers affecting young men. Although the evidence for genetic predisposition to TGCTs in humans is compelling, the genetic control of susceptibility is poorly understood. The 129S1/SvImJ (129/Sv) inbred Strain of mice is an excellent model for studying TGCT susceptibility. We previously reported a new mouse Strain, the 129.MOLF-Chr19 Chromosome Substitution Strain, which develops spontaneous TGCTs at a high frequency (70-80%) as compared with the much lower rate in the 129/Sv Strain (5%). To characterize the genetic control of TGCT susceptibility, we created a panel of single- and double-congenic Strains derived from 129.MOLF-Chr19. The frequency of TGCTs in these Strains suggests that several genes with additive and epistatic effects located at distinct sites on Chromosome 19 control susceptibility. However, an alternative interpretation involving epigenesis is based on a striking correlation between TGCT frequency and the length of the MOLF-derived congenic segment, regardless of their chromosomal location on Chr 19 in each congenic Strain. We also show that bilateral TGCT cases result from the coincidental co-occurrence of unilateral TGCTs rather than from the action of distinct genes that control susceptibility to bilateral versus unilateral TGCT cases. Finally, we propose that these TGCTs result from disrupted testicular and spermatogenic developmental programs.
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Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 Chromosome Substitution Strain
Nature Genetics, 1999Co-Authors: Angabin Matin, Gayle B. Collin, Yoshinobu Asada, Don S. Varnum, Joseph H. NadeauAbstract:Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 Chromosome Substitution Strain
Karlyne M. Reilly - One of the best experts on this subject based on the ideXlab platform.
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Chr 19A/J modifies tumor resistance in a sex- and parent-of-origin-specific manner
Mammalian Genome, 2009Co-Authors: Jessica C. Walrath, Kristi Fox, Erika Truffer, Octavio A. Quiñones, W. Gregory Alvord, Karlyne M. ReillyAbstract:Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2, that influence resistance to PNSTs in the Nf1−/+;Trp53−/+cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a Chromosome Substitution Strain, and further show that a modifier locus (or loci) on Chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on Chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of Chromosome Substitution Strains to study genetic modifiers.
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Chr 19^A/J modifies tumor resistance in a sex- and parent-of-origin-specific manner
Mammalian Genome, 2009Co-Authors: Jessica C. Walrath, Kristi Fox, Erika Truffer, W. Gregory Alvord, Octavio A. Quiñones, Karlyne M. ReillyAbstract:Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2 , that influence resistance to PNSTs in the Nf1 −/+; Trp53 −/+ cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a Chromosome Substitution Strain, and further show that a modifier locus (or loci) on Chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on Chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of Chromosome Substitution Strains to study genetic modifiers.
Jessica C. Walrath - One of the best experts on this subject based on the ideXlab platform.
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Chr 19A/J modifies tumor resistance in a sex- and parent-of-origin-specific manner
Mammalian Genome, 2009Co-Authors: Jessica C. Walrath, Kristi Fox, Erika Truffer, Octavio A. Quiñones, W. Gregory Alvord, Karlyne M. ReillyAbstract:Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2, that influence resistance to PNSTs in the Nf1−/+;Trp53−/+cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a Chromosome Substitution Strain, and further show that a modifier locus (or loci) on Chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on Chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of Chromosome Substitution Strains to study genetic modifiers.
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Chr 19^A/J modifies tumor resistance in a sex- and parent-of-origin-specific manner
Mammalian Genome, 2009Co-Authors: Jessica C. Walrath, Kristi Fox, Erika Truffer, W. Gregory Alvord, Octavio A. Quiñones, Karlyne M. ReillyAbstract:Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2 , that influence resistance to PNSTs in the Nf1 −/+; Trp53 −/+ cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a Chromosome Substitution Strain, and further show that a modifier locus (or loci) on Chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on Chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of Chromosome Substitution Strains to study genetic modifiers.
Chen Hsin Albert Yu - One of the best experts on this subject based on the ideXlab platform.
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candidate genes on murine Chromosome 8 are associated with susceptibility to staphylococcus aureus infection in mice and are involved with staphylococcus aureus septicemia in humans
PLOS ONE, 2017Co-Authors: Felix Mba Medie, Batu K Sharmakuinkel, Lawrence P Park, William K Scott, Hitesh Deshmukh, Ephraim L Tsalik, Christopher W Woods, Chen Hsin Albert YuAbstract:We previously showed that Chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome Substitution Strain 8 (CSS8) mice, which have Chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on Chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780–88103009 (GRCm38/mm10) on A/J Chromosome 8 that was linked to S. aureus susceptibility. All genes on the QTL (n~ 102) were further analyzed by three different strategies: 1) different expression in susceptible (A/J) and resistant (C57BL/6J) mice only in response to S. aureus, 2) consistently different expression in both uninfected and infected states between the two Strains, and 3) damaging non-synonymous SNPs in either Strain. Eleven candidate genes from the QTL region were significantly differently expressed in patients with S. aureus infection vs healthy human subjects. Four of these 11 genes also exhibited significantly different expression in S. aureus-challenged human neutrophils: Ier2, Crif1, Cd97 and Lyl1. CD97 ligand binding was evaluated within peritoneal neutrophils from A/J and C57BL/6J. CD97 from A/J had stronger CD55 but weaker integrin α5β1 ligand binding as compared with C57BL/6J. Because CD55/CD97 binding regulates immune cell activation and cytokine production, and integrin α5β1 is a membrane receptor for fibronectin, which is also bound by S. aureus, Strain-specific differences could contribute to susceptibility to S. aureus. Down-regulation of Crif1 with siRNA was associated with increased host cell apoptosis among both naive and S. aureus-infected bone marrow-derived macrophages. Specific genes in A/J Chromosome 8, including Cd97 and Crif1, may play important roles in host defense against S. aureus.
Ephraim L Tsalik - One of the best experts on this subject based on the ideXlab platform.
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candidate genes on murine Chromosome 8 are associated with susceptibility to staphylococcus aureus infection in mice and are involved with staphylococcus aureus septicemia in humans
PLOS ONE, 2017Co-Authors: Felix Mba Medie, Batu K Sharmakuinkel, Lawrence P Park, William K Scott, Hitesh Deshmukh, Ephraim L Tsalik, Christopher W Woods, Chen Hsin Albert YuAbstract:We previously showed that Chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome Substitution Strain 8 (CSS8) mice, which have Chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on Chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780–88103009 (GRCm38/mm10) on A/J Chromosome 8 that was linked to S. aureus susceptibility. All genes on the QTL (n~ 102) were further analyzed by three different strategies: 1) different expression in susceptible (A/J) and resistant (C57BL/6J) mice only in response to S. aureus, 2) consistently different expression in both uninfected and infected states between the two Strains, and 3) damaging non-synonymous SNPs in either Strain. Eleven candidate genes from the QTL region were significantly differently expressed in patients with S. aureus infection vs healthy human subjects. Four of these 11 genes also exhibited significantly different expression in S. aureus-challenged human neutrophils: Ier2, Crif1, Cd97 and Lyl1. CD97 ligand binding was evaluated within peritoneal neutrophils from A/J and C57BL/6J. CD97 from A/J had stronger CD55 but weaker integrin α5β1 ligand binding as compared with C57BL/6J. Because CD55/CD97 binding regulates immune cell activation and cytokine production, and integrin α5β1 is a membrane receptor for fibronectin, which is also bound by S. aureus, Strain-specific differences could contribute to susceptibility to S. aureus. Down-regulation of Crif1 with siRNA was associated with increased host cell apoptosis among both naive and S. aureus-infected bone marrow-derived macrophages. Specific genes in A/J Chromosome 8, including Cd97 and Crif1, may play important roles in host defense against S. aureus.