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CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis 总被引:13,自引:0,他引:13
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Rahman P Bartlett S Siannis F Pellett FJ Farewell VT Peddle L Schentag CT Alderdice CA Hamilton S Khraishi M Tobin Y Hefferton D Gladman DD 《American journal of human genetics》2003,73(3):677-681
A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA. 相似文献
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The IgG1hybridoma antibody, 91.9H, was originally raised against sulfated
mucins isolated from normal human colonic mucosa. Previous studies have
shown that the 91.9H antigen is expressed on normal colonic epithelial
cells and the sulfomucins that they produce, but not in the normal small
intestine and stomach. Tissue-specific changes occur in 91.9H antigen
expression in disease: the antigen diminishes in colonic carcinomas,
whereas in regions of gastric mucosa showing intestinal metaplasia and in
gastric carcinomas, the antigen is expressed as a "neo-antigen." This
report is concerned with elucidation, by the neoglycolipid technology, of
the determinant recognized by antibody 91.9H using sulfated and sialyl
oligosaccharides of Lewisa(Lea) and Lextypes, and analogs that lack
sulfate, sialic acid, or fucose. Binding experiments with the lipid-linked
oligosaccharides immobilized on chromatograms or on microwells, and
inhibition of binding experiments with free oligosaccharides based on di-,
tri- and tetrasaccharide backbones, show that the 91.9H antigenic
determinant is based on a trisaccharide backbone, and consists of the
3'-sulfated Leatetrasaccharide sequence, which is a potent ligand for the
E- and L-selectins. The antibody gives a relatively low signal with the
3'-sulfated non-fucosylated backbone, and has no detectable cross- reaction
with the 3'-sulfated Lexisomer, nor with sialyl-Leaand - Lexanalogues.
Antibody 91.9H is a valuable addition, therefore, to the repertoire of
reagents for mapping details of the distribution, and determining the
relative importance of sulfated and sialyl oligosaccharides as ligands for
the selectins, in normal and pathological epithelia and endothelia.
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S Senthilvel B Jayashree V Mahalakshmi P Sathish Kumar S Nakka T Nepolean CT Hash 《BMC plant biology》2008,8(1):119
Background
Pearl millet [Pennisetum glaucum (L.) R. Br.] is a staple food and fodder crop of marginal agricultural lands of sub-Saharan Africa and the Indian subcontinent. It is also a summer forage crop in the southern USA, Australia and Latin America, and is the preferred mulch in Brazilian no-till soybean production systems. Use of molecular marker technology for pearl millet genetic improvement has been limited. Progress is hampered by insufficient numbers of PCR-compatible co-dominant markers that can be used readily in applied breeding programmes. Therefore, we sought to develop additional SSR markers for the pearl millet research community. 相似文献26.
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Tineke E Buffart Melanie Louw Nicole CT van Grieken Marianne Tijssen Beatriz Carvalho Bauke Ylstra Heike Grabsch Chris JJ Mulder Cornelis JH van de Velde Schalk W van der Merwe Gerrit A Meijer 《BMC medical genomics》2011,4(1):7
Background
Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.Methods
DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.Results
Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.Conclusions
Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.28.
C T Schentag H J Dean J S Winter 《Human biology; an international record of research》1989,61(2):263-269
Using the Valk knemometer, lower leg length (LLL) was assessed relative to changes in the positioning of the upper leg. Lowering the chair height of the knemometer resulted in a more acute angle between the upper and lower leg and a decrease in LLL. This decrease in measurement was attributed to changes in the anatomical surface of the knee underlying the measuring platform as a result of increasing the acuity of the leg angle. Based on four different leg positions, the average change in LLL per centimeter change in chair height was 0.607 mm in a child sample of 50, and 0.655 mm in an adult sample of 20. The difference in chair height with the leg angle at 90 degrees and the lowest chair height possible, ranged from 12.3 to 30.3 mm, relative to lower leg length. This meant the longest leg in the study had a LLL measurement differing by 19.8 mm between these two positions. Due to the effect of leg position, we advised the use of a standard method of measuring LLL with respect to leg angle. Given the difficulties in accurately measuring leg angle with current available tools, we advise the most acute angle. 相似文献
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Positive selection driving the evolution of a gene of male reproduction, Acp26Aa, of Drosophila: II. Divergence versus polymorphism 总被引:5,自引:1,他引:4
The evolution of the gene for a male ejaculatory protein, Acp26Aa, has been
shown to be driven by positive selection when nonsibling species in the
Drosophila melanogaster subgroup are compared. To know if selection has
been operating in the recent past and to understand the details of its
dynamics, we obtained DNA sequences of Acp26Aa and the nearby Acp26Ab gene
from 39 D. melanogaster chromosomes. Together with the 10 published
sequences, we analyzed 49 sequences from five populations in four
continents. The southern African population is somewhat differentiated from
all other populations, but its nucleotide diversity is lower at these two
loci. We find the following results for Acp26Aa: (1) The R: S (replacement
: silent changes) ratio is significantly higher in the between-species
comparisons than in the within-species data by the McDonald and Kreitman
test. Positive selection is probably responsible for the excess of amino
acid replacements between species. (2) However, within-species nucleotide
diversity is high. Neither the Tajima test nor the Fu and Li test indicates
a reduction in nucleotide diversity due to positive selection in the recent
past. (3) The newly derived nucleotides in D. melanogaster are at high
frequency significantly more often than predicted by the neutral
equilibrium. Since the nearby Acp26Ab gene does not show these patterns,
these observations cannot be attributed to the characteristics of this
chromosomal region. We suggest that positive selection is active, but may
be weak, for each amino acid change in the Acp26Aa gene.
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