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  • Online Resource  (5)
  • Proceedings of the National Academy of Sciences  (5)
  • 1
    Online Resource
    Online Resource
    Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes
    Proceedings of the National Academy of Sciences ; 2000
    In:  Proceedings of the National Academy of Sciences Vol. 97, No. 3 ( 2000-02), p. 1172-1177
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 3 ( 2000-02), p. 1172-1177
    Abstract: The identification of the cystic fibrosis transmembrane conductance regulator gene ( CFTR ) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous advances in elucidating the function of the encoded protein and the physiological basis of cystic fibrosis. However, numerous areas of cystic fibrosis biology require additional investigation, some of which would be facilitated by information about the long-range sequence context of the CFTR gene. For example, the latter might provide clues about the sequence elements responsible for the temporal and spatial regulation of CFTR expression. We thus sought to establish the sequence of the chromosomal segments encompassing the human CFTR and mouse Cftr genes, with the hope of identifying conserved regions of biologic interest by sequence comparison. Bacterial clone-based physical maps of the relevant human and mouse genomic regions were constructed, and minimally overlapping sets of clones were selected and sequenced, eventually yielding ≈1.6 Mb and ≈358 kb of contiguous human and mouse sequence, respectively. These efforts have produced the complete sequence of the ≈189-kb and ≈152-kb segments containing the human CFTR and mouse Cftr genes, respectively, as well as significant amounts of flanking DNA. Analyses of the resulting data provide insights about the organization of the CFTR / Cftr genes and potential sequence elements regulating their expression. Furthermore, the generated sequence reveals the precise architecture of genes residing near CFTR / Cftr , including one known gene ( WNT2 / Wnt2 ) and two previously unknown genes that immediately flank CFTR / Cftr .
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.97.3.1172
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Automated cell lineage tracing in Caenorhabditis elegans
    Proceedings of the National Academy of Sciences ; 2006
    In:  Proceedings of the National Academy of Sciences Vol. 103, No. 8 ( 2006-02-21), p. 2707-2712
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 8 ( 2006-02-21), p. 2707-2712
    Abstract: The invariant cell lineage and cell fate of Caenorhabditis elegans provide a unique opportunity to decode the molecular mechanisms of animal development. To exploit this opportunity, we have developed a system for automated cell lineage tracing during C. elegans embryogenesis, based on 3D, time-lapse imaging and automated image analysis. Using ubiquitously expressed histone–GFP fusion protein to label cells/nuclei and a confocal microscope, the imaging protocol captures embryogenesis at high spatial (31 planes at 1 μm apart) and temporal (every minute) resolution without apparent effects on development. A set of image analysis algorithms then automatically recognizes cells at each time point, tracks cell movements, divisions and deaths over time and assigns cell identities based on the canonical naming scheme. Starting from the four-cell stage (or earlier), our software, named starrynite , can trace the lineage up to the 350-cell stage in 25 min on a desktop computer. The few errors of automated lineaging can then be corrected in a few hours with a graphic interface that allows easy navigation of the images and the reported lineage tree. The system can be used to characterize lineage phenotypes of genes and/or extended to determine gene expression patterns in a living embryo at the single-cell level. We envision that this automation will make it practical to systematically decipher the developmental genes and pathways encoded in the genome of C. elegans .
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0511111103
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2006
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 28 ( 2018-07-10), p. 7386-7391
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 28 ( 2018-07-10), p. 7386-7391
    Abstract: Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 × 10 −5 /gene per generation in C. elegans , the highest for any species to date. The rate of gene deletion is sixfold lower (5 × 10 −6 /gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1801930115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    More on the sequencing of the human genome
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 6 ( 2003-03-18), p. 3022-3024
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 6 ( 2003-03-18), p. 3022-3024
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0634129100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    On the sequencing of the human genome
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 6 ( 2002-03-19), p. 3712-3716
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 6 ( 2002-03-19), p. 3712-3716
    Abstract: Two recent papers using different approaches reported draft sequences of the human genome. The international Human Genome Project (HGP) used the hierarchical shotgun approach, whereas Celera Genomics adopted the whole-genome shotgun (WGS) approach. Here, we analyze whether the latter paper provides a meaningful test of the WGS approach on a mammalian genome. In the Celera paper, the authors did not analyze their own WGS data. Instead, they decomposed the HGP's assembled sequence into a “perfect tiling path”, combined it with their WGS data, and assembled the merged data set. To study the implications of this approach, we perform computational analysis and find that a perfect tiling path with 2-fold coverage is sufficient to recover virtually the entirety of a genome assembly. We also examine the manner in which the assembly was anchored to the human genome and conclude that the process primarily depended on the HGP's sequence-tagged site maps, BAC maps, and clone-based sequences. Our analysis indicates that the Celera paper provides neither a meaningful test of the WGS approach nor an independent sequence of the human genome. Our analysis does not imply that a WGS approach could not be successfully applied to assemble a draft sequence of a large mammalian genome, but merely that the Celera paper does not provide such evidence.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.042692499
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
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