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排序方式: 共有335条查询结果,搜索用时 18 毫秒
1.
Mutations in the basement membrane collagen gene COL4A5 cause the progressive renal glomerular nephropathy and typical hearing
loss that occur in X-linked Alport syndrome. Nearly all cases involve distinct mutations, as expected for an X-linked disease
that significantly reduces the fitness of affected males. A few exceptional COL4A5 mutations appear to be associated with
a reduced disease severity and may account for a significant proportion of late-onset Alport syndrome in populations where
a founder effect has occurred. The novel mutation reported here, COL4A5 arg1677gln, has been detected in three independently
ascertained Ashkenazi-American families, causes a relatively mild form of nephritis with typical onset in the fourth or fifth
decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.
Received: 14 October 1996 / Revised: 11 December 1996 相似文献
2.
3.
A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. 总被引:5,自引:1,他引:4
D. F. Barker C. J. Pruchno X. Jiang C. L. Atkin E. M. Stone J. C. Denison P. R. Fain M. C. Gregory 《American journal of human genetics》1996,58(6):1157-1165
Mutations in the COL4A5 gene, located at Xq22, cause Alport syndrome (AS), a nephritis characterized by progressive deterioration of the glomerular basement membrane and usually associated with progressive hearing loss. We have identified a novel mutation, L1649R, present in 9 of 121 independently ascertained families. Affected males shared the same haplotype of eight polymorphic markers tightly linked to COL4A5, indicating common ancestry. Genealogical studies place the birth of this ancestor >200 years ago. The L1649R mutation is a relatively common cause of Alport syndrome in the western United States, in part because of the rapid growth and migratory expansion of mid-nineteenth-century pioneer populations carrying the gene. L1649R affects a highly conserved residue in the NC1 domain, which is involved in key inter- and intramolecular interactions, but results in a relatively mild disease phenotype. Renal failure in an L1649R male typically occurs in the 4th or 5th decade and precedes the onset of significant hearing loss by approximately 10 years. 相似文献
4.
5.
Localization of Mouse Hepatitis Virus Nonstructural Proteins and RNA Synthesis Indicates a Role for Late Endosomes in Viral Replication 总被引:15,自引:0,他引:15 下载免费PDF全文
Yvonne van der Meer Eric J. Snijder Jessika C. Dobbe Sibylle Schleich Mark R. Denison Willy J. M. Spaan Jacomine Krijnse Locker 《Journal of virology》1999,73(9):7641-7657
The aim of the present study was to define the site of replication of the coronavirus mouse hepatitis virus (MHV). Antibodies directed against several proteins derived from the gene 1 polyprotein, including the 3C-like protease (3CLpro), the putative polymerase (POL), helicase, and a recently described protein (p22) derived from the C terminus of the open reading frame 1a protein (CT1a), were used to probe MHV-infected cells by indirect immunofluorescence (IF) and electron microscopy (EM). At early times of infection, all of these proteins showed a distinct punctate labeling by IF. Antibodies to the nucleocapsid protein also displayed a punctate labeling that largely colocalized with the replicase proteins. When infected cells were metabolically labeled with 5-bromouridine 5'-triphosphate (BrUTP), the site of viral RNA synthesis was shown by IF to colocalize with CT1a and the 3CLpro. As shown by EM, CT1a localized to LAMP-1 positive late endosomes/lysosomes while POL accumulated predominantly in multilayered structures with the appearance of endocytic carrier vesicles. These latter structures were also labeled to some extent with both anti-CT1a and LAMP-1 antibodies and could be filled with fluid phase endocytic tracers. When EM was used to determine sites of BrUTP incorporation into viral RNA at early times of infection, the viral RNA localized to late endosomal membranes as well. These results demonstrate that MHV replication occurs on late endosomal membranes and that several nonstructural proteins derived from the gene 1 polyprotein may participate in the formation and function of the viral replication complexes. 相似文献
6.
Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes 总被引:23,自引:2,他引:21
Statistical methods for computing the standard errors of the branching
points of an evolutionary tree are developed. These methods are for the
unweighted pair-group method-determined (UPGMA) trees reconstructed from
molecular data such as amino acid sequences, nucleotide sequences,
restriction-sites data, and electrophoretic distances. They were applied to
data for the human, chimpanzee, gorilla, orangutan, and gibbon species.
Among the four different sets of data used, DNA sequences for an
895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the
most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979)
gave the least reliable one. The DNA sequence data suggested that the
chimpanzee is the closest and that the gorilla is the next closest to the
human species. The orangutan and gibbon are more distantly related to man
than is the gorilla. This topology of the tree is in agreement with that
for the tree obtained from chromosomal studies and DNA-hybridization
experiments. However, the difference between the branching point for the
human and the chimpanzee species and that for the gorilla species and the
human-chimpanzee group is not statistically significant. In addition to
this analysis, various factors that affect the accuracy of an estimated
tree are discussed.
相似文献
7.
A comparative description of mitochondrial DNA differentiation in selected avian and other vertebrate genera 总被引:14,自引:1,他引:13
Levels of mitochondrial DNA (mtDNA) sequence divergence between species
within each of several avian (Anas, Aythya, Dendroica, Melospiza, and
Zonotrichia) and nonavian (Lepomis and Hyla) vertebrate genera were
compared. An analysis of digestion profiles generated by 13-18 restriction
endonucleases indicates little overlap in magnitude of mtDNA divergence for
the avian versus nonavian taxa examined. In 55 interspecific comparisons
among the avian congeners, the fraction of identical fragment lengths (F)
ranged from 0.26 to 0.96 (F = 0.46), and, given certain assumptions, these
translate into estimates of nucleotide sequence divergence (p) ranging from
0.007 to 0.088; in 46 comparisons among the fish and amphibian congeners, F
values ranged from 0.00 to 0.36 (F = 0.09), yielding estimates of P greater
than 0.070. The small mtDNA distances among avian congeners are associated
with protein-electrophoretic distances (D values) less than approximately
0.2, while the mtDNA distances among assayed fish and amphibian congeners
are associated with D values usually greater than 0.4. Since the
conservative pattern of protein differentiation previously reported for
many avian versus nonavian taxa now appears to be paralleled by a
conservative pattern of mtDNA divergence, it seems increasingly likely that
many avian species have shared more recent common ancestors than have their
nonavian taxonomic counterparts. However, estimates of avian divergence
times derived from mtDNA- and protein-calibrated clocks cannot readily be
reconciled with some published dates based on limited fossil remains. If
the earlier paleontological interpretations are valid, then protein and
mtDNA evolution must be somewhat decelerated in birds. The empirical and
conceptual issues raised by these findings are highly analogous to those in
the long-standing debate about rates of molecular evolution and times of
separation of ancestral hominids from African apes.
相似文献
8.
Nonneutral evolution of tandem repeats in the mitochondrial DNA control region of lagomorphs 总被引:7,自引:0,他引:7
Casane D; Dennebouy N; de Rochambeau H; Mounolou JC; Monnerot M 《Molecular biology and evolution》1997,14(8):779-789
The mitochondrial DNA of the European rabbit (Oryctolagus cuniculus)
contains a tandem array of 153-bp repeats in the vicinity of the
replication origin of the H-stand. Variation among molecules in the number
of these repeats results in inter- and intraindividual length polymorphism
(heteroplasmy). Generally, in an individual, one predominant molecular type
is observed, the others representing a low percentage of the mtDNA content.
At the tissue level, we observe a particular distribution of this
polymorphism in the gonads compared with liver, kidneys, or brain, implying
a relationship between the differentiation status of the cells and the
types of new mtDNA molecules which appear and accumulate during lifetime.
Similar tandem repeats were also found in the mtDNA noncoding region of
European hares (Lepus europaeus), a cottontail (Sylvilagus floridanus), and
a pika (Ochotona rufescens). The lengths and the sequences of these units
evolve rapidly and in a concerted way, but the number of repeats is
maintained in a narrow range, and an internal 20-bp segment is highly
conserved. Constraints restrict the evolution of the primary sequence of
these repeated units, the number of which is probably controlled by a
stabilizing selection.
相似文献
9.
Identification of polypeptides encoded in open reading frame 1b of the putative polymerase gene of the murine coronavirus mouse hepatitis virus A59. 总被引:11,自引:9,他引:2 下载免费PDF全文
M R Denison P W Zoltick J L Leibowitz C J Pachuk S R Weiss 《Journal of virology》1991,65(6):3076-3082
The polypeptides encoded in open reading frame (ORF) 1b of the mouse hepatitis virus A59 putative polymerase gene of RNA 1 were identified in the products of in vitro translation of genome RNA. Two antisera directed against fusion proteins containing sequences encoded in portions of the 3'-terminal 2.0 kb of ORF 1b were used to immunoprecipitate p90, p74, p53, p44, and p32 polypeptides. These polypeptides were clearly different in electrophoretic mobility, antiserum reactivity, and partial protease digestion pattern from viral structural proteins and from polypeptides encoded in the 5' end of ORF 1a, previously identified by in vitro translation. The largest of these polypeptides had partial protease digestion patterns similar to those of polypeptides generated by in vitro translation of a synthetic mRNA derived from the 3' end of ORF 1b. The polypeptides encoded in ORF 1b accumulated more slowly during in vitro translation than polypeptides encoded in ORF 1a. This is consistent with the hypothesis that translation of gene A initiates at the 5' end of ORF 1a and that translation of ORF 1b occurs following a frameshift at the ORF 1a-ORF 1b junction. The use of in vitro translation of genome RNA and immunoprecipitation with antisera directed against various regions of the polypeptides encoded in gene A should make it possible to study synthesis and processing of the putative coronavirus polymerase. 相似文献
10.
Olivier Koole Julie A Denison Joris Menten Sharon Tsui Fred Wabwire-Mangen Gideon Kwesigabo Modest Mulenga Andrew Auld Simon Agolory Ya Diul Mukadi Eric van Praag Kwasi Torpey Seymour Williams Jonathan Kaplan Aaron Zee David R Bangsberg Robert Colebunders 《PloS one》2016,11(1)