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R C Eisensmith Y Okano M Dasovich T Wang F Güttler H Lou P Guldberg U Lichter-Konecki D S Konecki E Svensson 《American journal of human genetics》1992,51(6):1355-1365
Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12n1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population. 相似文献
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【目的】研究pH信号通路(Pal)在重寄生真菌盾壳霉与寄主核盘菌互作过程中的作用。【方法】从盾壳霉全基因组信息中分析获得了6个Pal相关基因CmpalA、CmpalB、CmpalC、CmpalF、CmpalH和CmpalI的全编码序列和氨基酸序列,通过PEG介导的原生质转化技术获得了CmpalA、CmpalB、CmpalC、CmpalF和CmpalH等5个基因的敲除突变体,分析这些敲除突变体与野生型在菌落培养性状、重寄生能力、降解草酸能力、产生抗真菌物质能力等方面的差异。【结果】与野生型相比,在pH 6–8的条件下,5个Pal相关基因敲除突变体的菌丝生长受到显著抑制,这说明缺失Pal相关基因使盾壳霉对高pH值环境更加敏感。菌核重寄生试验发现5个Pal相关基因敲除突变体的重寄生能力均显著低于野生型。qRT-PCR试验结果表明,敲除Pal相关基因之后导致重寄生相关酶基因Cmch1、Cmg1和Cmsp1的表达量显著降低,而且pH信号通路下游的CmpacC基因的表达量也显著降低。Pal相关基因敲除突变体在pH 6条件下对草酸盐的降解能力显著高于野生型,同时这5个突变体在pH 8条件下产生抗真菌物质能力也显著高于野生型。【结论】pH信号通路相关基因的缺失影响盾壳霉对环境pH的响应。pH信号通路在盾壳霉与核盘菌互作中发挥重要作用,不仅影响盾壳霉的重寄生作用,而且还影响盾壳霉的草酸降解作用和抗真菌作用。 相似文献
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Crystallization of the first three domains of the human insulin-like growth factor-1 receptor. 下载免费PDF全文
N. M. McKern M. Lou M. J. Frenkel A. Verkuylen J. D. Bentley G. O. Lovrecz N. Ivancic T. C. Elleman T. P. Garrett L. J. Cosgrove C. W. Ward 《Protein science : a publication of the Protein Society》1997,6(12):2663-2666
The insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor of central importance in cell proliferation. A fragment (residues 1-462) comprising the L1-cysteine rich-L2 domains of the human IGF-1R ectodomain has been overexpressed in glycosylation-deficient Lec8 cells and has been affinity-purified via a c-myc tag followed by gel filtration. The fragment was recognized by two anti-IGF-1R monoclonal antibodies, 24-31 and 24-60, but showed no detectable binding of IGF-1 or IGF-2. Isocratic elution of IGF-1R/462 on anion-exchange chromatography reduced sample heterogeneity, permitting the production of crystals that diffracted to 2.6 A resolution with cell dimensions a = 77.0 A, b = 99.5 A, c = 120.1 A, and space group P2(1)2(1)2(1). 相似文献
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The isolation layer of the graft union is a changeable component. It is formed and thickened during the early stage (Fig. 6) and disrupted, thinned and even disappeared durmg tile later stage of development of the graft (Fig. 1, 2, 14). A number of vesicles, paramarat bodies (Fig. 3, 5, 8, 9, 11, 13, 19), multivesicular bodies (Fig. 4, 15, 16, 18, 20) and concentric membrane bodies (Fig. 7) are observed in callus 'beside the isolation layer during both stages of development based on transmission electron microscopy. The paramural body comprises invagination of plasmalemma containing numerous vesicles and/or tubules situated between the cell wall and the plasmalemma. The multivesicular body is a organelle about 0.5-μm in diameter with a single membrane surrounding several smaller single vesicles. It is possible that multivesicular body and/or single iesicles transverse the plasmalemma to produce paramural body. The figures show that the paramural bodies appear always beside the isolalion layer at the different stages of development of the graft union and the multivesicular bodies appear mostly near the region where plasmodesmata are secondarily formed between the stock and the scion (Fig. 15, 17, 20). This may reflect that paramural body and multivesi- cular body, as well as single vesicles, are capable of performing vesicular transport. The deposition and reabsorption of material of the isolation layer occur due to vesicular transport. All the above facts seem to indicate that paramural body, multivesicular body and single vesicles can be both endocytotic and exocytotic. The present study supports the theory of vesicular transport, and authors suggest that transcellular cytosis occurs not only through plasmodesmata but also through plasmalemma in oapoplast. The single vesicles, paramural bodies and multivesicular bodies take an active part in the transport process of symplast-apoplast-symplast. 相似文献
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