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33.
SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.
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W A Sweetman B Rash B Sykes P Beighton J T Hecht B Zabel J T Thomas R Boot-Handford M E Grant G A Wallis 《American journal of human genetics》1992,51(4):841-849
Type X collagen is a homotrimeric, short chain, nonfibrillar collagen that is expressed exclusively by hypertrophic chondrocytes at the sites of endochondral ossification. The distribution and pattern of expression of the type X collagen gene (COL10A1) suggests that mutations altering the structure and synthesis of the protein may be responsible for causing heritable forms of chondrodysplasia. We investigated whether mutations within the human COL10A1 gene were responsible for causing the disorders achondroplasia, hypochondroplasia, pseudoachondroplasia, and thanatophoric dysplasia, by analyzing the coding regions of the gene by using PCR and the single-stranded conformational polymorphism technique. By this approach, seven sequence changes were identified within and flanking the coding regions of the gene of the affected persons. We demonstrated that six of these sequence changes were not responsible for causing these forms of chondrodysplasia but were polymorphic in nature. The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families. This lack of segregation suggests that mutations within or near the COL10A1 locus are not responsible for these disorders. The seventh sequence change resulted in a valine-to-methionine substitution in the carboxyl-terminal domain of the molecule and was identified in only two hypochondroplasic individuals from a single family. Segregation analysis in this family was inconclusive, and the significance of this substitution remains uncertain. 相似文献
34.
Matthias Laska 《Primates; journal of primatology》1996,37(4):457-465
The purpose of this study was to test the influence of sex, age, social rank, matriline membership, posture, and visual and
tactual motor control on manual preferences inSaimiri sciureus. A well-established social group of 12 squirrel monkeys, aged 2 to 14 yrs and consisting of two matrilines with social rank
known for each animal, was presented with four different food-reaching tasks and assessed for hand preferences with a minimum
of 100 reaches per animal.
Frequency of occurrence of hand preferences at the group level and degree of hand preferences at the individual level depended
on posture and on whether the reaching act took place under visual or tactual guidance. Sex, age, social rank, and matriline
membership were not found to determine frequency of occurrence, direction or degree of hand preferences with the exception
of one task in which a significant negative correlation between the degree of hand preference and age was found. Nine out
of 12 monkeys showed task-dependent changes in the hand they used preferentially while only three animals preferred the same
hand in all four tasks. Significant preferences for the use of right or left hand on a given task were distributed almost
equally between individuals. Thus, the results of this study suggest task-specific demands like posture and/or whether reaching
was visually or tactually guided to be the major correlates of hand preferences in food-reaching tasks in squirrel monkeys. 相似文献
35.
Exclusion of epidermal growth factor and high-resolution physical mapping across the Rieger syndrome locus. 总被引:5,自引:1,他引:4
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E. V. Semina N. A. Datson N. J. Leysens B. U. Zabel J. C. Carey G. I. Bell P. Bitoun C. Lindgren T. Stevenson R. R. Frants G. van Ommen J. C. Murray 《American journal of human genetics》1996,59(6):1288-1296
We have evaluated the 4q25-4q26 region where the autosomal dominant disorder Rieger syndrome has been previously mapped by linkage. We first excluded epidermal growth factor as a candidate gene by carrying out SSCP analysis of each of its 24 exons using a panel of seven unrelated individuals with Rieger syndrome. No evidence for etiologic mutations was detected in these individuals, although four polymorphic variants were identified, including three that resulted in amino acid changes. We next made use of two apparently balanced translocations, one familial and one sporadic, to identify a narrow physical localization likely to contain the gene or to be involved in regulation of gene function. Somatic cell hybrids were established from individuals with these balanced translocations, and these hybrids were used as a physical mapping resource for, first, preliminary mapping of the translocation breakpoints using known sequence tagged sites from chromosome 4 and then, after creating YAC and cosmids contigs encompassing the region, for fine mapping of those breakpoints. A cosmid contig spanning these breakpoints was identified and localized the gene to within approximately 150 kb of D4S193 on chromosome 4. The interval between the two independent translocations is approximately 50 kb in length and provides a powerful resource for gene identification. 相似文献
36.
Folkert Reck Ernst Meinjohanns Matthias Springer Roland Wilkens Johannes A. L. M. Van Dorst Hans Paulsen Gabriele Möller Inka Brockhausen Harry Schachter 《Glycoconjugate journal》1994,11(3):210-216
UDP-GlcNAc: Man1-6R (1-2)-N-acetylglucosaminyltransferase II (GlcNAc-T II; EC 2.4.1.143) is a key enzyme in the synthesis of complexN-glycans. We have tested a series of synthetic analogues of the substrate Man1-6(GlcNAc1-2Man1-3)Man-O-octyl as substrates and inhibitors for rat liver GlcNAc-T II. The enzyme attachesN-acetylglucosamine in 1-2 linkage to the 2-OH of the Man1-6 residue. The 2-deoxy analogue is a competitive inhibitor (K
i=0.13mm). The 2-O-methyl compound does not bind to the enzyme presumably due to steric hindrance. The 3-, 4- and 6-OH groups are not essential for binding or catalysis since the 3-, 4- and 6-deoxy and -O-methyl derivatives are all good substrates. Increasing the size of the substituent at the 3-position to pentyl and substituted pentyl groups causes competitive inhibition (K
i=1.0–2.5mm). We have taken advantage of this effect to synthesize two potentially irreversible GlcNAc-T II inhibitors containing a photolabile 3-O-(4,4-azo)pentyl group and a 3-O-(5-iodoacetamido)pentyl group respectively. The data indicate that none of the hydroxyls of the Man1-6 residue are essential for binding although the 2- and 3-OH face the catalytic site of the enzyme. The 4-OH group of the Man-O-octyl residue is not essential for binding or catalysis since the 4-deoxy derivative is a good substrate; the 4-O-methyl derivative does not bind. This contrasts with GlcNAc-T I which cannot bind to the 4-deoxy-Man- substrate analogue. The data are compatible with our previous observations that a bisectingN-acetylglucosamine at the 4-OH position prevents both GlcNAc-T I and GlcNAc-T II catalysis. However, in the case of GlcNAc-T II, the bisectingN-acetylglucosamine prevents binding due to steric hindrance rather than to removal of an essential OH group. The 3-OH of the Man1-3 is an essential group for GlcNAc-T II since the 3-deoxy derivative does not bind to the enzyme. The trisaccharide GlcNAc1-2Man1-3Man-O-octyl is a good inhibitor (K
i=0.9mm). The above data together with previous studies indicate that binding of the GlcNAc1-2Man1-3Man- arm of the branched substrate to the enzyme is essential for catalysis.
Abbreviations: GlcNAc-T I, UDP-GlcNAc:Man1-3R (1-2)-N-acetylglucosaminyltransferase I (EC 2.4.1.101); GlcNAc-T II, UDP-GlcNAc:Man1-6R (1-2)-N-acetylglucosaminyltransferase II (EC 2.4.1.143); MES, 2-(N-morpholino)ethane sulfonic acid monohydrate. 相似文献
37.
Gellerich Frank Norbert Kapischke Matthias Kunz Wolfram Neumann Wolfram Kuznetsov Andrey Brdiczka Dieter Nicolay Klaas 《Molecular and cellular biochemistry》1994,133(1):85-104
Summary Cytosolic proteins as components of the physiological mitochondrial environment were substituted by dextrans added to media normally used for incubation of isolated mitochondria. Under these conditions the volume of the intermembrane space decreases and the contact sites between the both mitochondrial membranes increase drastically. These morphological changes are accompanied by a reduced permeability of the mitochondrial outer compartment for adenine nucleotides as it was shown by extensive kinetic studies of mitochondrial enzymes (oxidative phosphorylation, mi-creatine kinase, mi-adenylate kinase). The decreased permeability of the mitochondrial outer membrane causes increased rate dependent concentration gradients in the micromolar range for adenine nucleotides between the intermembrane space and the extramitochondrial space. Although all metabolites crossing the outer membrane exhibit the same concentration gradients, considerable compartmentations are detectable for ADP only due to its low extramitochondrial concentration. The consequences of ADP-compartmentation in the mitochondrial intermembrane space for ADP-channelling into the mitochondria are discussed. 相似文献
38.
39.
Egbert J. Boekema Arjen F. Boonstra Jan P. Dekker Matthias Rögner 《Journal of bioenergetics and biomembranes》1994,26(1):17-29
Electron microscopy (EM) in combination with image analysis is a powerful technique to study protein structure at low- and high resolution. Since electron micrographs of biological objects are very noisy, substantial improvement of image quality can be obtained by averaging individual projections. Crystallographic and noncrystallographic averaging methods are available and have been applied to study projections of the large protein complexes embedded in photosynthetic membranes from cyanobacteria and higher plants. Results of EM on monomeric and trimeric Photosystem I complexes, on monomeric and dimeric Photosystem II complexes, and on the monomeric cytochromeb6/f complex are discussed. 相似文献
40.
Matthias Liebergesell Alexander Steinbüchel 《Applied microbiology and biotechnology》1993,38(4):493-501
From a genomic library of Thiocystis violaceae strain 2311 in L47, two adjacent EcoRI restriction fragments of 5361 base pairs (bp) and of 1978 bp were cloned. The 5361-bp EcoRI restriction fragment hybridized with a DNA fragment harbouring the Alcaligenes eutrophus poly(3-hydroxyalkanoate) (PHA) synthase operon (phbCAB) and restored the ability to synthesize and accumulate PHA in PHA-negative mutants derived from A. eutrophus. The nucleotide sequence analysis of both fragments revealed five open-reading frames (ORFs); at least three of them are probably relevant for PHA biosynthesis. The amino acid sequences of the putative proteins deduced from these genes indicate that they encode a -ketothiolase [phbA
Tv, relative molecular mass (Mr) 40850], which exhibited 87.3% amino acid identify with the -ketothiolase from Chromatium vinosum. The amino acid sequences of the putative proteins deduced from ORF2Tv (Mr 41 450) and phbC
Tv (Mr 39 550), which were located upstream of and antilinear to phbA
Tv, exhibited 74.7% and 87.6% amino acid identify, respectively, with the corresponding gene products of C. vinosum. Downstream of and antilinear to phbC
Tv was located ORF5, which encodes for a protein of high relative molecular mass (Mr 76428) of unknown function. With respect to the divergent organisation of ORF2Tv and phbC
Tv on one side and of phbA
Tv on the other side and from the homologies of the putative gene products, this region of the T. violaceae genome resembled very much the corresponding region of C. vinosum, which was identified recently.
Correspondence to: A. Steinbüchel 相似文献