Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways.

Gene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a causally connected way. To demonstrate that individual variant genes from connected pathways result in similar but distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of 2 related but distinct pathways, gluconeogenesis and glycolysis, we show that individual causal paths in gene networks give rise to discrete phenotypic outcomes resulting from perturbations of glycolytic and gluconeogenic genes. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes

Immunoglobulin heavy chain gene rearrangement and transcription in murine t cell hybrids and t lymphomas.

Статья посвящена творчеству современного русского поэта Германа Лукомникова и его формальным и стилевым поискам в области альтернативной поэзии. Работая с редкими и экспериментальными поэтическими формами, поэт сочетает классические образцы с нелитературными явлениями и находит новую поэзию реальности, требующую нового способа выражения за рамками традиционных представлений

The alpha-globin pseudogene on mouse chromosome 17 is closely linked to H-2.

DNA sequences homologous to adult alpha-globin genes are dispersed in the mouse. Two functional genes are tightly linked on chromosome 11. Pseudogenes have been assigned to chromosomes 15 and 17 by analysis of interspecies somatic cell hybrids. We have now further characterized the second of these pseudogenes, Hba-a4. The gene is highly polymorphic, with three forms occurring in a panel of 15 inbred strains and a fourth occurring in an inbred strain derived from M. m. molossinus. Analysis of Hba-a4 alleles in CXB, BXH, and AKXL recombinant inbred strains placed Hba-a4 6.60 +/- 3.14 cM centromeric to H-2. Analysis of congenic mouse strains confirmed the linkage and the gene order. Hba-a4 is the first mammalian dispersed pseudogene to be localized in a linkage map, and should provide a useful marker for the region of chromosome 17 proximal to H-2