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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
5.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4
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Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
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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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![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
9.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
10.