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141.
K. J. Collins K. G. Foster J. L. Hubbard 《Cellular and molecular life sciences : CMLS》1970,26(12):1313-1314
Zusammenfassung Nachweis, dass Natriumretention bei der menschlichen Temperaturregulation und in den exokrinen Schweissdrüsen der Handflächen von Aldosteron verursacht wird; dies im Unterschied zu den Drüsen in Katzenpfoten, welche charakteristischerweise vom exokrinen Sekretionsprozess des duktalen Ionenwechsels nicht beeinflusst werden und weder auf Aldosteron noch auf Blutung reagieren. 相似文献
142.
143.
Multiple forms of human brain mitochondrial monoamine oxidase 总被引:11,自引:0,他引:11
144.
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome 总被引:36,自引:0,他引:36
Eriksson M Brown WT Gordon LB Glynn MW Singer J Scott L Erdos MR Robbins CM Moses TY Berglund P Dutra A Pak E Durkin S Csoka AB Boehnke M Glover TW Collins FS 《Nature》2003,423(6937):293-298
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing. 相似文献
145.
Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors 总被引:14,自引:0,他引:14
Zardo G Tiirikainen MI Hong C Misra A Feuerstein BG Volik S Collins CC Lamborn KR Bollen A Pinkel D Albertson DG Costello JF 《Nature genetics》2002,32(3):453-458
Aberrant methylation of CpG islands and genomic deletion are two predominant mechanisms of gene inactivation in tumorigenesis, but the extent to which they interact is largely unknown. The lack of an integrated approach to study these mechanisms has limited the understanding of tumor genomes and cancer genes. Restriction landmark genomic scanning (RLGS; ref. 1) is useful for global analysis of aberrant methylation of CpG islands, but has not been amenable to alignment with deletion maps because the identity of most RLGS fragments is unknown. Here, we determined the nucleotide sequence and exact chromosomal position of RLGS fragments throughout the genome using the whole chromosome of origin of the fragments and in silico restriction digestion of the human genome sequence. To study the interaction of these gene-inactivation mechanisms in primary brain tumors, we integrated RLGS-based methylation analysis with high-resolution deletion maps from microarray-based comparative genomic hybridization (array CGH; ref. 3). Certain subsets of gene-associated CpG islands were preferentially affected by convergent methylation and deletion, including genes that exhibit tumor-suppressor activity, such as CISH1 (encoding SOCS1; ref. 4), as well as genes such as COE3 that have been missed by traditional non-integrated approaches. Our results show that most aberrant methylation events are focal and independent of deletions, and the rare convergence of these mechanisms can pinpoint biallelic gene inactivation without the use of positional cloning. 相似文献
146.
Collins N Poot RA Kukimoto I García-Jiménez C Dellaire G Varga-Weisz PD 《Nature genetics》2002,32(4):627-632
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin. 相似文献
147.
Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome,a complex human obesity syndrome 总被引:11,自引:0,他引:11
Mykytyn K Nishimura DY Searby CC Shastri M Yen HJ Beck JS Braun T Streb LM Cornier AS Cox GF Fulton AB Carmi R Lüleci G Chandrasekharappa SC Collins FS Jacobson SG Heckenlively JR Weleber RG Stone EM Sheffield VC 《Nature genetics》2002,31(4):435-438
Bardet-Biedl syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism. Individuals with BBS are also at increased risk for diabetes mellitus, hypertension and congenital heart disease. What was once thought to be a homogeneous autosomal recessive disorder is now known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13 p12 (BBS3), 15q22.3 q23 (BBS4), 2q31 (BBS5) and 20p12 (BBS6). There has been considerable interest in identifying the genes that underlie BBS, because some components of the phenotype are common. Cases of BBS mapping ro BBS6 are caused by mutations in MKKS; mutations in this gene also cause McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly and congenital heart defects). In addition, we recently used positional cloning to identify the genes underlying BBS2 (ref. 16) and BBS4 (ref. 17). The BBS6 protein has similarity to a Thermoplasma acidophilum chaperonin, whereas BBS2 and BBS4 have no significant similarity to chaperonins. It has recently been suggested that three mutated alleles (two at one locus, and a third at a second locus) may be required for manifestation of BBS (triallelic inheritance). Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance. 相似文献
148.
149.
The human T-cell receptor alpha-chain gene maps to chromosome 14 总被引:7,自引:0,他引:7
M K Collins P N Goodfellow N K Spurr E Solomon G Tanigawa S Tonegawa M J Owen 《Nature》1985,314(6008):273-274
The T-cell receptor for antigen has been identified as a disulphide-linked heterodimeric glycoprotein of relative molecular mass (Mr) 90,000 comprising an alpha- and a beta-chain. The availability of complementary DNA clones encoding mouse and human beta-chains has allowed a detailed characterization of the genomic organization of the beta-chain gene family and has revealed that functional beta-chain genes in T cells are generated from recombination events involving variable (V), diversity (D), joining (J) and constant (C) gene segments. Recently, cDNA clones encoding mouse and human alpha-chains have been described; the sequences of these clones have indicated that functional alpha-chain genes are also generated from multiple gene segments. It is possible that chromosomal translocations involving T-cell receptor alpha- and beta-chain genes have a role in T-cell neoplasms in much the same way as translocations involving immunoglobulin genes are associated with oncogenic transformation in B cells. In the latter case, the chromosomal localization of the immunoglobulin genes provided one of the first indications of the involvement of such translocations in oncogenic transformation. The chromosomal assignment of the alpha- and beta-chain genes may, therefore, provide equally important clues for T-cell neoplastic transformation. The chromosomal location of the mouse and human beta-chain gene family has been determined: the murine gene lies on chromosome 6 (refs 12, 13) whereas the human gene is located on chromosome 7 (refs 13, 14). Here we use a cDNA clone encoding the human alph-chain to map the corresponding gene to chromosome 14. 相似文献
150.
Species diversity enhances ecosystem functioning through interspecific facilitation. 总被引:42,自引:0,他引:42
Facilitation between species is thought to be a key mechanism by which biodiversity affects the rates of resource use that govern the efficiency and productivity of ecosystems; however, there is no direct empirical evidence to support this hypothesis. Here we show that increasing the species diversity of a functional group of aquatic organisms induces facilitative interactions, leading to non-additive changes in resource consumption. We increased the richness and evenness of suspension-feeding caddisfly larvae (Insecta, Trichoptera) in stream mesocosms and found that the increased topographical complexity of the benthic habitat alters patterns of near-bed flow such that the feeding success of individuals is enhanced. Species diversity reduces 'current shading' (that is, the deceleration of flow from upstream to downstream neighbours), allowing diverse assemblages to capture a greater fraction of suspended resources than is caught by any species monoculture. The fundamental nature of this form of hydrodynamic facilitation suggests that it is broadly applicable to freshwater and marine habitats; in addition, it has several analogues in terrestrial ecosystems where fluxes of energy and matter can be influenced by biophysical complexity. Thus, changes in species diversity may alter the probability of positive species interactions, resulting in disproportionately large changes in the functioning of ecosystems. 相似文献