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Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping 总被引:14,自引:0,他引:14
INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing beta-cells of the pancreas. Family and population studies indicate that predisposition is probably polygenic. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3, 4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR-DQ haplotypes, whose frequencies vary between races. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition. 相似文献
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Quantification of modelling uncertainties in a large ensemble of climate change simulations 总被引:17,自引:0,他引:17
Murphy JM Sexton DM Barnett DN Jones GS Webb MJ Collins M Stainforth DA 《Nature》2004,430(7001):768-772
Comprehensive global climate models are the only tools that account for the complex set of processes which will determine future climate change at both a global and regional level. Planners are typically faced with a wide range of predicted changes from different models of unknown relative quality, owing to large but unquantified uncertainties in the modelling process. Here we report a systematic attempt to determine the range of climate changes consistent with these uncertainties, based on a 53-member ensemble of model versions constructed by varying model parameters. We estimate a probability density function for the sensitivity of climate to a doubling of atmospheric carbon dioxide levels, and obtain a 5-95 per cent probability range of 2.4-5.4 degrees C. Our probability density function is constrained by objective estimates of the relative reliability of different model versions, the choice of model parameters that are varied and their uncertainty ranges, specified on the basis of expert advice. Our ensemble produces a range of regional changes much wider than indicated by traditional methods based on scaling the response patterns of an individual simulation. 相似文献
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J E Itzhaki M A Barnett A B MacCarthy V J Buckle W R Brown A C Porter 《Nature genetics》1992,2(4):283-287
Novel approaches to the structural and functional analysis of mammalian chromosomes would be possible if the gross structure of the chromosomes in living cells could be engineered. Controlled modifications can be engineered by conventional targeting techniques based on homologous recombination. Large but uncontrolled modifications can be made by the integration of cloned human telomeric DNA. We describe here the combined use of gene targeting and telomere-mediated chromosome breakage to generate a defined truncation of a human chromosome. Telomeric DNA was targeted to the 6-16 gene on the short arm of chromosome 1 in a human cell line. Molecular and cytogenetic analyses showed that, of eight targeted clones that were isolated, one clone had the predicted truncation of chromosome 1. 相似文献
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The immobilization antigens (i-antigens) of Paramecium, large polypeptides of relative molecular mass approximately 300,000, are located on the cell surface. Each i-antigen is encoded by a different unlinked gene, and no more than one gene is expressed at a time. The proteins and the mRNAs and genes encoding them are readily isolated. Here we report the nucleotide sequence of three regions of the A i-antigen gene from stock 51 of Paramecium tetraurelia. Surprisingly, all reading frames contain TAA and TAG stop codons, even though there is evidence that one reading frame of these sequences codes for the i-antigen. We suggest that in Paramecium UAA and UAG code for amino acids, instead of serving as translational stops as they do in all other organisms. 相似文献
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Cardiovascular development: towards biomedical applicability 总被引:4,自引:0,他引:4
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