The Experts below are selected from a list of 320997 Experts worldwide ranked by ideXlab platform
Jan M Van Deursen - One of the best experts on this subject based on the ideXlab platform.
-
whole chromosome instability caused by bub1 insufficiency drives tumoriGenesis through tumor suppressor Gene Loss of heterozygosity
Cancer Cell, 2009Co-Authors: Darren J Baker, Fang Jin, Karthik B Jeganathan, Jan M Van DeursenAbstract:Genetic alterations that promote chromosome missegregation have been proposed to drive tumoriGenesis through Loss of whole chromosomes containing key tumor suppressor Genes. To test this unproven idea, we bred Bub1 mutant mice that inaccurately segregate their chromosomes onto p53(+/-), Apc(Min/+), Rb(+/-), or Pten(+/-) backgrounds. Bub1 insufficiency predisposed p53(+/-) mice to thymic lymphomas and Apc(Min/+) mice to colonic tumors. These tumors consistently lacked the nonmutated tumor suppressor allele but had gained a copy of the mutant allele. In contrast, Bub1 insufficiency had no impact on tumoriGenesis in Rb(+/-) mice and inhibited prostatic intraepithelial neoplasia formation in Pten(+/-) mice. Thus, Bub1 insufficiency can drive tumor formation through tumor suppressor Gene Loss of heterozygosity, but only in restricted Genetic and cellular contexts.
Marta L Wayne - One of the best experts on this subject based on the ideXlab platform.
-
ohno s peril of hemizygosity revisited Gene Loss dosage compensation and mutation
Genome Biology and Evolution, 2013Co-Authors: David W Hall, Marta L WayneAbstract:We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of Gene Loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving Gene dose for wild-type alleles. We then consider the evolution of DC in response to Gene Loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, Genes from longer metabolic pathways should be lost first, as halving these Genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit Loss of Genes in short pathways.
-
Ohno’s “Peril of Hemizygosity” Revisited: Gene Loss, Dosage Compensation, and Mutation
Genome Biology and Evolution, 2012Co-Authors: David W Hall, Marta L WayneAbstract:We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of Gene Loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving Gene dose for wild-type alleles. We then consider the evolution of DC in response to Gene Loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, Genes from longer metabolic pathways should be lost first, as halving these Genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit Loss of Genes in short pathways.
Karl H Plate - One of the best experts on this subject based on the ideXlab platform.
-
up regulation of hypoxia inducible factors hif 1alpha and hif 2alpha under normoxic conditions in renal carcinoma cells by von hippel lindau tumor suppressor Gene Loss of function
Oncogene, 2000Co-Authors: Marion Krieg, Richard Haas, Hiltrud Brauch, Till Acker, Ingo Flamme, Karl H PlateAbstract:Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor Gene Loss of function
Darren J Baker - One of the best experts on this subject based on the ideXlab platform.
-
whole chromosome instability caused by bub1 insufficiency drives tumoriGenesis through tumor suppressor Gene Loss of heterozygosity
Cancer Cell, 2009Co-Authors: Darren J Baker, Fang Jin, Karthik B Jeganathan, Jan M Van DeursenAbstract:Genetic alterations that promote chromosome missegregation have been proposed to drive tumoriGenesis through Loss of whole chromosomes containing key tumor suppressor Genes. To test this unproven idea, we bred Bub1 mutant mice that inaccurately segregate their chromosomes onto p53(+/-), Apc(Min/+), Rb(+/-), or Pten(+/-) backgrounds. Bub1 insufficiency predisposed p53(+/-) mice to thymic lymphomas and Apc(Min/+) mice to colonic tumors. These tumors consistently lacked the nonmutated tumor suppressor allele but had gained a copy of the mutant allele. In contrast, Bub1 insufficiency had no impact on tumoriGenesis in Rb(+/-) mice and inhibited prostatic intraepithelial neoplasia formation in Pten(+/-) mice. Thus, Bub1 insufficiency can drive tumor formation through tumor suppressor Gene Loss of heterozygosity, but only in restricted Genetic and cellular contexts.
David W Hall - One of the best experts on this subject based on the ideXlab platform.
-
ohno s peril of hemizygosity revisited Gene Loss dosage compensation and mutation
Genome Biology and Evolution, 2013Co-Authors: David W Hall, Marta L WayneAbstract:We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of Gene Loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving Gene dose for wild-type alleles. We then consider the evolution of DC in response to Gene Loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, Genes from longer metabolic pathways should be lost first, as halving these Genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit Loss of Genes in short pathways.
-
Ohno’s “Peril of Hemizygosity” Revisited: Gene Loss, Dosage Compensation, and Mutation
Genome Biology and Evolution, 2012Co-Authors: David W Hall, Marta L WayneAbstract:We explore the evolutionary origins of dosage compensation (DC) in sex chromosomes in the context of metabolic control theory. We consider first the cost of Gene Loss (hemizygosity) per se in reducing flux, and examine two relationships between flux and fitness (linear and Gaussian) to calculate a fitness cost of hemizygosity. Recognizing that new sex chromosomes are derived from autosomes, we also calculate the cost of unmasking deleterious mutations segregating on the nascent sex chromosomes as loci become hemizygous. The importance of deleterious mutations to the fitness cost of hemizygosity depends on their frequency, and on the relative costs of halving Gene dose for wild-type alleles. We then consider the evolution of DC in response to Gene Loss, and include a cost of overexpression (i.e., DC such that expression exceeds the wild-type homozygote). Even with costs to excess flux, hypomorphic mutations can cause the optimal level of DC to be higher than 2-fold when the absolute cost of hemizygosity is small. Finally, we propose a three-step model of DC evolution: 1) once recombination ceases and the Y begins to deteriorate, Genes from longer metabolic pathways should be lost first, as halving these Genes does not drastically reduce flux or, thereby, fitness; 2) both the cost of hemizygosity and the presence of hypomorphic mutations will drive an increase in expression, that is, DC; 3) existing DC will now permit Loss of Genes in short pathways.