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841.
Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome 总被引:52,自引:0,他引:52
Prader-Willi syndrome (PWS) is the most common form of dysmorphic genetic obesity associated with mental retardation. About 60% of cases have a cytological deletion of chromosome 15q11q13 (refs 2, 3). These deletions occur de novo exclusively on the paternal chromosome. By contrast, Angelman syndrome (AS) is a very different clinical disorder and is also associated with deletions of region 15q11q13 (refs 6-8), indistinguishable from those in PWS except that they occur de novo on the maternal chromosome. The parental origin of the affected chromosomes 15 in these disorders could, therefore, be a contributory factor in determining their clinical phenotypes. We have now used cloned DNA markers specific for the 15q11q13 subregion to determine the parental origin of chromosome 15 in PWS individuals not having cytogenetic deletions; these individuals account for almost all of the remaining 40% of PWS cases. Probands in two families displayed maternal uniparental disomy for chromosome 15q11q13. This is the first demonstration that maternal heterodisomy--the presence of two different chromosome 15s derived from the mother--can be associated with a human genetic disease. The absence of a paternal contribution of genes in region 15q11q13, as found in PWS deletion cases, rather than a mutation in a specific gene(s) in this region may result in expression of the clinical phenotype. Thus, we conclude that a gene or genes in region 15q11q13 must be inherited from each parent for normal human development. 相似文献
842.
The telomeric ends of eukaryotic chromosomes are composed of simple repeating sequences in which one DNA strand contains short tracts of guanine residues alternating with short tracts of A/T-rich sequences. The guanine-rich strand is always oriented in a 5'-3' direction towards the end of the chromosome and is extended to produce a 3' overhang of about two repeating units in species where the telomeric terminus is known. This overhang has been implicated in the formation of several unusual intra-and intermolecular DNA structures, although none of these structures has been characterized fully. We now report that oligonucleotides encoding Tetrahymena telomeres dimerize to form stable complexes in solution. This salt-dependent dimerization is mediated entirely by the 3'-terminal telomeric overhang (TT-GGGGTTGGGG) and produces complexes in which the N7 position of every guanine in the overhangs is chemically inaccessible. We therefore propose that telomeric DNA dimerizes by hydrogen bonding between two intramolecular hairpin loops, to form antiparallel quadruplexes containing cyclic guanine base tetrads. These novel hairpin dimers may be important in telomere association and recombination and could also provide a general mechanism for pairing two double helices in other recombinational processes. 相似文献
843.
844.
Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor 总被引:17,自引:0,他引:17
The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures. We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions. 相似文献
845.
J. N. D. Wurpel 《Cellular and molecular life sciences : CMLS》1994,50(5):475-478
This study investigates the effect of the gamma-aminobutyric acid (GABAB) agonist, baclofen, on amygdala kindling in adult rats. Baclofen has been reported to be anticonvulsant in a variety of seizure models and prevents kindling in immature rats. These experiments describe the effects of baclofen (2, 5 and 10 mg/kg, i.p.) on the afterdischarge threshold and kindling rate. Baclofen, 10 mg/kg, significantly increased the afterdischarge threshold in the amygdala. Baclofen at 5 and 10 mg/kg, retarded the rate of kindling as measured by the number of stimuli required to advance to subsequent seizure stages. These results suggest that baclofen may decrease the local excitability of the amygdala and retard the rate of seizure spread (or generalization) throughout the brain. Baclofen, acting at GABAB receptors exerts an anticonvulsant effect on amygdala kindling in these experiments. 相似文献
846.
Gene inactivation triggered by recognition between DNA repeats 总被引:15,自引:0,他引:15
This chapter focuses on phenomena of gene inactivation resulting from the presence of repeated gene copies within the genome of plants and fungi, and on their possible relationships to homologous DNA-DNA interactions. Emphasis is given to two related premeiotic processes: Methylation Induced Premeiotically (MIP) and Repeat-Induced Point mutation (RIP) which take place in the fungiAscobolus immersus andNeurospora crassa, respectively. The relationships between these processes and genetic recombination are discussed. 相似文献
847.
In vitro ecdysteroid production by dissociated Y-organ cells of the shore crabCarcinus maenas was characterized during short-term incubations. Under optimized conditions (M199 adjusted to crab osmolality and with the addition of 10% foetal calf serum), ecdysteroid production by dispersed cells increased linearly during 4-hour incubations, with little intra-assay variation. 25-deoxyecdysone was mainly produced. PurifiedCarcinus molt inhbiting hormone (CamMIH) produced a dose-dependent inhibition of ecdysteroid production by dispersed cells. The cells were about 50 times more sensitive than whole glands to MIH. Other structurally-related peptides were tested. 相似文献
848.
T. J. Hall 《Cellular and molecular life sciences : CMLS》1994,50(11-12):1048-1053
Interleukin-1 and tumor necrosis factor-alpha are potent, multifunctional cytokine mediators of inflammation and immune responses that are produced primarily by activated monocytes and macrophages. Three published papers by different groups have shown that heat shock and chemical stress with heavy metal salts or sulfhydryl reagents, all of which induce the expression of heat shock protein 70 (hsp70), concomitantly inhibit the production of these cytokines in human monocytes and mouse macrophages activated by lipopolysaccharide. These papers are reviewed and discussed in some detail. Other studies suggest that various anti-inflammatory drugs, including acetylsalicyclic acid, auranofin and dexamethasone, can also facilitate HSP expression in macrophages. However, while these studies are interesting, it is clear that not a great deal of work has been done and/or published in this area. Since many pharmaceutical companies are developing cytokine synthesis inhibitors as potential anti-inflammatory drugs, one aim of this article is to emphasize that understanding the molecular mechanism(s) that lead to increased HSP expression and decreased cytokine biosynthesis may assist in achieving this goal. 相似文献
849.
Li/MgO甲烷氧化偶联催化剂引入铌的氧化物可降低活性温度,750℃以下便达到最高C2烃产率。铌与锂、镁有多种结合方式,引入方法对活性测试结果有重要影响。铌不与镁紧密结合且分布于锂、镁之间时作用最好。 相似文献
850.