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  • 1
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2006
    In:  Genome Research Vol. 16, No. 4 ( 2006-04), p. 550-556
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 16, No. 4 ( 2006-04), p. 550-556
    Abstract: Modern molecular biology has brought many new tools to the geneticist as well as an exponentially expanding database of genomes and new genes for study. Of particular use in the analysis of these genes is the synthetic gene, a nucleotide sequence designed to the specifications of the investigator. Typically, synthetic genes encode the same product as the gene of interest, but the synthetic nucleotide sequence for that protein may contain modifications affecting expression or base composition. Other desirable changes typically involve the revision of restriction sites. Designing synthetic genes by hand is a time-consuming and error-prone process that may involve several computer programs. We have developed a tools environment that combines many modules to provide a platform for rapid synthetic gene design for multikilobase sequences. We have used GeneDesign to successfully design a synthetic Ty1 element and a large variety of other synthetic sequences. GeneDesign has been implemented as a publicly accessible Web-based resource and can be found at http://slam.bs.jhmi.edu/gd.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2006
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2006
    In:  Nature Methods Vol. 3, No. 11 ( 2006-11), p. 903-907
    In: Nature Methods, Springer Science and Business Media LLC, Vol. 3, No. 11 ( 2006-11), p. 903-907
    Type of Medium: Online Resource
    ISSN: 1548-7091 , 1548-7105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 2163081-1
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2005
    In:  Genome Research Vol. 15, No. 8 ( 2005-08), p. 1073-1078
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 15, No. 8 ( 2005-08), p. 1073-1078
    Abstract: The L1 retrotransposon is the most highly successful autonomous retrotransposon in mammals. This prolific genome parasite may on occasion benefit its host through genome rearrangements or adjustments of host gene expression. In examining possible effects of L1 elements on host gene expression, we investigated whether a full-length L1 element inserted in the antisense orientation into an intron of a cellular gene may actually split the gene's transcript into two smaller transcripts: (1) a transcript containing the upstream exons and terminating in the major antisense polyadenylation site (MAPS) of the L1, and (2) a transcript derived from the L1 antisense promoter (ASP) that includes the downstream exons of the gene. Bioinformatic analysis and experimental follow-up provide evidence for this L1 “gene-breaking” hypothesis. We identified three human genes apparently “broken” by L1 elements, as well as 12 more candidate genes. Most of the inserted L1 elements in our 15 candidate genes predate the human/chimp divergence. If indeed split, the transcripts of these genes may in at least one case encode potentially interacting proteins, and in another case may encode novel proteins. Gene-breaking represents a new mechanism through which L1 elements remodel mammalian genomes.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2005
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Royal Society of Chemistry (RSC) ; 2008
    In:  Molecular BioSystems Vol. 4, No. 7 ( 2008), p. 726-
    In: Molecular BioSystems, Royal Society of Chemistry (RSC), Vol. 4, No. 7 ( 2008), p. 726-
    Type of Medium: Online Resource
    ISSN: 1742-206X , 1742-2051
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2008
    detail.hit.zdb_id: 2188635-0
    SSG: 12
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2006
    In:  Proceedings of the National Academy of Sciences Vol. 103, No. 47 ( 2006-11-21), p. 17632-17637
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 47 ( 2006-11-21), p. 17632-17637
    Abstract: Mobile elements are important components of our genomes, with diverse and significant effects on phenotype. Not only can transposons inactivate genes by direct disruption and shuffle the genome through recombination, they can also alter gene expression subtly or powerfully. Currently active transposons are highly polymorphic in host populations, including, among hundreds of others, L1 and Alu elements in humans and Ty1 elements in yeast. For this reason, we wished to develop a simple genome-wide method for identifying all transposons in any given sample. We have designed a transposon insertion site profiling chip (TIP-chip), a microarray intended for use as a high-throughput technique for mapping transposon insertions. By selectively amplifying transposon flanking regions and hybridizing them to the array, we can locate all transposons present in a sample. We have tested the TIP-chip extensively to map Ty1 retrotransposon insertions in yeast and have achieved excellent results in two laboratory strains as well as in evolved Ty1 high-copy strains. We are able to identify all of the theoretically detectable transposons in the FY2 lab strain, with essentially no false positives. In addition, we mapped many new transposon copies in the high-copy Ty1 strain and determined its Ty1 insertion pattern.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    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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  • 6
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2006
    In:  Proceedings of the National Academy of Sciences Vol. 103, No. 49 ( 2006-12-05), p. 18662-18667
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 49 ( 2006-12-05), p. 18662-18667
    Abstract: Long interspersed element type 1 (L1) retrotransposons are ubiquitous mammalian mobile elements and potential tools for in vivo mutagenesis; however, native L1 elements are relatively inactive in mice when introduced as transgenes. We have previously described a synthetic L1 element, ORFeus , containing two synonymously recoded ORFs relative to mouse L1. It is significantly more active for retrotransposition in cell culture than all native L1 elements tested. To study its activity in vivo , we developed a transgenic mouse model in which ORFeus expression was controlled by a constitutive heterologous promoter, and we established definitive evidence for ORFeus retrotransposition activity both in germ line and somatic tissues. Germ line retrotransposition frequencies resulting in 0.33 insertions per animal are seen among progeny of ORFeus donor element heterozygotes derived from a single founder, representing a 〉 20-fold increase over native L1 elements. We observe somatic transposition events in 100% of the ORFeus donor-containing animals, and an average of 17 different insertions are easily recovered from each animal; modeling suggests that the number of somatic insertions per animal exceeds this number by perhaps several orders of magnitude. Nearly 200 insertions were precisely mapped, and their distribution in the mouse genome appears random relative to transcription units and guanine-cytosine content. The results suggest that ORFeus may be developed into useful tools for in vivo mutagenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    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
    Location Call Number Limitation Availability
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