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41.
Kraytsberg Y Kudryavtseva E McKee AC Geula C Kowall NW Khrapko K 《Nature genetics》2006,38(5):518-520
Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA (mtDNA) molecules with deletions, we show that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions. Molecules with deletions are largely clonal within each neuron; that is, they originate from a single deleted mtDNA molecule that has expanded clonally. The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration. 相似文献
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The genetic basis of most conditions characterized by congenital contractures is largely unknown. Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal arthrogryposis. FSS and SHS mutations affect different myosin residues, demonstrating that MYH3 genotype is predictive of phenotype. A structure-function analysis shows that nearly all of the MYH3 mutations are predicted to interfere with myosin's catalytic activity. These results add to the growing body of evidence showing that congenital contractures are a shared outcome of prenatal defects in myofiber force production. Elucidation of the genetic basis of these syndromes redefines congenital contractures as unique defects of the sarcomere and provides insights about what has heretofore been a poorly understood group of disorders. 相似文献
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A single positively selected West Nile viral mutation confers increased virogenesis in American crows 总被引:1,自引:0,他引:1
Brault AC Huang CY Langevin SA Kinney RM Bowen RA Ramey WN Panella NA Holmes EC Powers AM Miller BR 《Nature genetics》2007,39(9):1162-1166
West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species. 相似文献
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Structural organization of the rat thy-1 gene 总被引:1,自引:0,他引:1
Thy-1 is a differentiation marker expressed predominantly on thymocytes, T cells and brain tissue. Its presence on murine peripheral T cells but not B cells has long been used to distinguish between these two populations of lymphocytes. Although analogues of Thy-1 have been described in several mammalian species, its tissue distribution in different species varies widely, precluding its use as T-cell-specific marker. The Thy-1 molecule is a cell-surface glycoprotein of relative molecular mass 18,000, one-third of which represents carbohydrate; the protein moieties of the rat and murine Thy-1 molecules have been sequenced and found to consist of 111 and 112 amino acids, respectively. An unusual aspect of Thy-1 is the apparent absence of a hydrophobic segment comparable to that observed in other membrane glycoproteins which would allow integration of Thy-1 within the membrane lipid bilayer. This has prompted speculation that Thy-1 is anchored to the cell surface by some other hydrophobic component such as glycolipid. Here we report the structure of thy-1 complementary DNA and genomic clones and describe the exon-intron organization of the gene. More importantly, our data indicate that Thy-1 is initially synthesized as a molecule of 142 amino acids, 31 amino acids longer at the carboxyl end than the Thy-1 molecule isolated and characterized by Campbell et al. An extremely hydrophobic region of 20 amino acids lies within this 31-amino acid stretch and may represent the transmembrane segment responsible for anchoring Thy-1 to the cell membrane. 相似文献
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线粒体DNA出现突变比预期快的结论,推动了新的法医学程序,却增加了有关进化事件断代的困难。leql年俄罗斯人挖掘出并检验了西伯利亚一座葬有9具骨殖的坟墓。有人认为那是俄罗斯本代沙皇尼古拉二世和家人及待从的遗骸,他们是1918年被行刑队枪杀的。但是有两人失踪,所以没有人能完全确认遗骸身份。lop年做了DNA试验--期望能够较快地得到结论--使之不再增加新的难解之秘。沙皇线粒体的一些DNA一细胞内的细胞器都有自己的DNA与他还活着的亲属们的DNA并不十分相符。法医学专家们认为大多数人只有一种线粒体DNA(mtDNA),但是沙皇却… 相似文献
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The small deciduous tree Celtis reticulata (neatleaf hackberry) reaches its northern limit in Idaho, where, contrary to most of its western range, it often occurs as an overstory dominantly. Two hundred fifty stands of this tree were sampled throughout Idaho. Celtis is slow-growing, averaging 4 m tall at 50 yr, and long-lived (to 300-400yr). It occurs in a variety of habitats, from riparian to rocky uplands. Trees grow best where topographically sheltered, such as in draws and narrow canyons, and were soils are loamy. Although plants grow more slowly as surface rock cover increases, stands are often associated with rock, with a mean surface cover of 39% rock. Differences in growth rates were unrelated to parent material and aspect. Most stands are reproducing, in spite of habitat degradation caused by overgrazing, alien plant invasion, and increasing fire frequencies. Stands are typically represented by one dominant cohort; however, young, even-aged stands are rare and are generally found along waterways on stream terraces or at the high-water line. Although slow growing, C. reticulata shows promise for land mangers interested in site enhancement. This native species is long-lived, produces fruit used by wildlife, and provides structural diversity in a semiarid landscape (with a maximum height o 12 m) in areas that are becoming increasingly dominated by exotic plant species. 相似文献
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