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排序方式: 共有411条查询结果,搜索用时 15 毫秒
1.
2.
A mutation in the insulin receptor gene that impairs transport of the receptor to the plasma membrane and causes insulin-resistant diabetes. 总被引:12,自引:1,他引:11
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D Accili C Frapier L Mosthaf C McKeon S C Elbein M A Permutt E Ramos E Lander A Ullrich S I Taylor 《The EMBO journal》1989,8(9):2509-2517
Insulin binds to a receptor on the cell surface, thereby triggering a biological response within the target cell. Mutations in the insulin receptor gene can render the cell resistant to the biological action of insulin. We have studied a family in which two sisters have a genetic form of insulin-resistant diabetes mellitus. The technique of homozygosity mapping has been used to demonstrate that the mutation causing diabetes in this consanguineous family is genetically linked to the insulin receptor gene. The two insulin-resistant sisters are homozygous for a mutation encoding substitution of valine for phenylalanine at position 382 in the alpha-subunit of the insulin receptor. Transfection of mutant insulin receptor cDNA into NIH3T3 cells demonstrated that the Val382 mutation impaired post-translational processing and retarded transport of the insulin receptor to the plasma membrane. Thus, the mutation causes insulin resistance by decreasing the number of insulin receptors on the surface of the patients' cells. 相似文献
3.
Genomic mapping by fingerprinting random clones: a mathematical analysis 总被引:44,自引:0,他引:44
Results from physical mapping projects have recently been reported for the genomes of Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans, and similar projects are currently being planned for other organisms. In such projects, the physical map is assembled by first "fingerprinting" a large number of clones chosen at random from a recombinant library and then inferring overlaps between clones with sufficiently similar fingerprints. Although the basic approach is the same, there are many possible choices for the fingerprint used to characterize the clones and the rules for declaring overlap. In this paper, we derive simple formulas showing how the progress of a physical mapping project is affected by the nature of the fingerprinting scheme. Using these formulas, we discuss the analytic considerations involved in selecting an appropriate fingerprinting scheme for a particular project. 相似文献
4.
Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. 总被引:47,自引:0,他引:47
H J Jacob K Lindpaintner S E Lincoln K Kusumi R K Bunker Y P Mao D Ganten V J Dzau E S Lander 《Cell》1991,67(1):213-224
The stroke-prone spontaneously hypertensive rat (SHRSP) is a well-characterized model for primary hypertension in humans. High blood pressure in SHRSP shows polygenic inheritance, but none of the loci responsible have previously been identified. To locate genes controlling this quantitative trait, we mapped a large collection of DNA polymorphisms in a cross between SHRSP and the normotensive WKY strain. Here we report strong genetic evidence that a gene, Bp1, having a major effect on blood pressure maps to rat chromosome 10 with a LOD score of 5.10 and is closely linked to the rat gene encoding angiotensin-converting enzyme (ACE), an enzyme that plays a major role in blood pressure homeostasis and is an important target of anti-hypertensive drugs. We also find significant, albeit weaker, linkage to a locus, Bp2, on chromosome 18. We discuss the implications of genetic dissection of quantitative disease-related phenotypes in mammals. 相似文献
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7.
Mom1 Is a Semi-Dominant Modifier of Intestinal Adenoma Size and Multiplicity in Min/+ Mice 总被引:5,自引:1,他引:4
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The intestinal tumor multiplicity in mice heterozygous for Apc(Min) is strongly modulated by genetic background. On the sensitive C57BL/6J (B6) background, mice develop large numbers of intestinal adenomas. The AKR/J (AKR) strain carries alleles that correlate with a strong reduction in tumor multiplicity. To study the effect of one of these modifiers, Mom1, we have generated a mouse line in which the AKR allele of Mom1 is carried on the sensitive B6 genetic background. This strain was produced by using a marker-assisted selection method to eliminate unlinked AKR alleles more rapidly. The application and efficiency of this method are discussed. We used this strain to determine that Mom1 affects both tumor multiplicity and tumor size in a semi-dominant fashion. 相似文献
8.
Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex 总被引:14,自引:1,他引:13
Two regions of the genome, a 1-kbp portion of the zeste locus and a 1.1-
kbp portion of the yolk protein 2 locus, were sequenced in six individuals
from each of four species: Drosophila melanogaster, D. simulans, D.
mauritiana, and D. sechellia. The species and strains were the same as
those of a previous study of a 1.9-kbp region of the period locus. No
evidence was found for recent balancing or directional selection or for the
accumulation of selected differences between species. Yolk protein 2 has a
high level of amino acid replacement variation and a low level of
synonymous variation, while zeste has the opposite pattern. This contrast
is consistent with information on gene function and patterns of codon bias.
Polymorphism levels are consistent with a ranking of effective population
sizes, from low to high, in the following order: D. sechellia, D.
melanogaster, D.mauritiana, and D. simulans. The apparent species
relationships are very similar to those suggested by the period locus
study. In particular, D. simulans appears to be a large population that is
still segregating variation that arose before the separation of D.
mauritiana and D. sechellia. It is estimated that the separation of
ancestral D. melanogaster from the other species occurred 2.5-3.4 Mya. The
separations of D. sechellia and D. mauritiana from ancestral D. simulans
appear to have occurred 0.58- 0.86 Mya, with D. mauritiana having diverged
from ancestral D. simulans 0.1 Myr more recently than D. sechellia.
相似文献
9.
10.
Hemin stimulates cAMP production in human peripheral blood mononuclear cells (PBMC). The kinetics are similar to that of hormone-induced cAMP generation, namely a rapid effect followed by a desensitization phase. Several experimental findings suggest that prostaglandins do not mediate this effect. First, macrophage depleted T and B cells purified by erythrocyte-rosetting were as responsive as unfractionated PBMC to hemin. Second, indomethacin, an inhibitor of prostaglandin synthesis, and meclofenamate, a prostaglandin E2 receptor antagonist, had no effect on hemin stimulated cAMP production. In addition, propranolol, a beta-adrenergic receptor antagonist, had no effect on hemin-stimulated cAMP production. We also examined structural analogues of hemin. Among the metalloporphyrins (Fe, Ni, Co, Zn and Sn) and protoporphyrin IX tested only hemin (Fe-protoporphyrin) was active in stimulating cAMP production. No correlation was found between the ability of metalloporphyrins to stimulate cAMP production and their ability to generate H2O2. The data indicate that hemin stimulates cAMP production by directly affecting lymphocytes and that prostaglandins do not mediate this effect. 相似文献