Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To develop the baboon model for molecular genetic studies of atherosclerosis, we have cloned and sequenced the baboon apolipoprotein E (apo E) gene. The baboon apo E gene encodes the E4 isoform with respect to specific amino acid positions, suggesting that the common epsilon 3 allele is not the primal human allele. Rather than accumulating predominantly synonymous nucleotide changes, 50% of substitutions in human and baboon apo E gene coding regions cause amino acid substitutions. However, comparisons of these apo E proteins show conservation of amphipathic helices required for apo E--lipid interactions. The human and baboon apo E genes have diverged less extensively than those from rat and mouse, providing further evidence for a slowing of molecular evolution in primate species. The baboon and rhesus monkey apo E genes (intron 2) contain two Alu repeats that are absent in the human gene, indicating insertion after the divergence of human and cercopithecine lineages, but before the baboon/rhesus divergence. S1 nuclease studies show that transcription of the baboon apo E gene starts at two different positions, one of which corresponds to the human gene start site. To examine linkage of apolipoprotein genes in the baboon genome, we have used a human cDNA probe to detect apo C-I gene sequences approximately 4 kb from the 3' end of the baboon apo E gene.
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PMID:The baboon apolipoprotein E gene: structure, expression, and linkage with the gene for apolipoprotein C-1. 322 Apr 72

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent smooth muscle cell mitogen of macrophage origin. It is expressed in a highly regulated fashion in vascular endothelial and smooth muscle cells, indicating a potentially important role for this gene in atherosclerosis. In addition, the HB-EGF precursor has recently been found to function as a receptor for diphtheria toxin. Using an HB-EGF cDNA probe, we cloned the human gene encoding HB-EGF. The HB-EGF gene contains six exons and five intervening sequences spanning 14 kb of DNA. By primer extension and S1 nuclease analysis, we located a major transcription start site (corresponding to an A residue) 14 bp beyond the 5' end of the HB-EGF cDNA. There were no TATAAA or CCAAT consensus sequences upstream of the transcription start site. The density of primer extension bands generated by RNA from endothelial cells treated with tumor necrosis factor-alpha (TNF-alpha) was 10 times higher than that of bands generated by the control, indicating that TNF-alpha increased the level of HB-EGF mRNA. Using transient reporter gene transfection experiments, we show that 2.0 kb of HB-EGF 5'-flanking sequence has promoter activity in bovine aortic endothelial cells. By analysis of DNA isolated from human-mouse somatic hybrid cell lines, we assign the HB-EGF gene to chromosome 5. By functional study, chromosome 5 has been associated with diphtheria toxin susceptibility.
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PMID:Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor. 834 98