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2017 | 66 | 3 | 343-350
Article title

Związek aktywności transpozonów line z wybranymi chorobami genetycznymi człowieka

Title variants
Activity of line transposons and selected genetic diseases
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Sekwencje LINE należą do grupy ruchomych elementów genetycznych w genomach eukariotycznych. Rozprzestrzeniają się w nich według modelu "kopiuj i wklej" za pośrednictwem RNA i odwrotnej transkryptazy. W genomie ludzkim zlokalizowano ponad 500 tys. kopii tych elementów, niemniej nieliczne z nich zachowują swoją aktywność. Jej konsekwencją jest destabilizacja struktury genomu powodująca zaburzenia ekspresji genów, alternatywnego splicingu czy aktywację alternatywnych promotorów. Transpozycja LINE to proces aktywny głównie we wczesnych stadiach embriogenezy, natomiast w prawidłowych komórkach somatycznych tłumiona jest za pomocą mechanizmów epigenetycznych. Zmiany w poziomie metylacji DNA tych elementów są jednym z głównych wskaźników ich aktywności wiązanej z licznymi chorobami genetycznymi. Najpełniej opisane zostały zależności między aktywnością LINE a różnymi postaciami nowotworów.
LINE transposons (Long Interspersed Nuclear Elements) are mobile, endogenous genetic elements widespread in eukaryotic genomes. Their ability to spread out with help of reverse transcriptase by using RNA intermediates indicates that they belong to autonomous retrotransposons. Original element is transcribed, then RNA undergoes reverse transcription and as a DNA fragment it is inserted into another part of the genome. Despite of the presence of over 500.000 of their copies in the human genome, majority of LINEs became inactive due to structural changes during the process of evolution. Sequences that retained their original function, play an important role in organization and functioning of genomes. Their activity results in destabilization of a genome structure, as a result of de novo insertions of LINEs and changes caused by homologous recombination between them. They can cause changes in the level of gene expression by interfering with alternative splicing (resulting in exon skipping or selecting cryptic splice sites), generating polyadenylation signals or providing alternative promoters. LINE retrotransposition is active mainly during the early stages of embryogenesis. In normal somatic cells this process is silenced by epigenetic mechanisms. Changes in DNA methylation levels of these elements is one of the main indicators of their activity associated with multiple genetic diseases. Correlations between LINE activity and multiple forms of neoplasms are mostly described in this paper.
Physical description
  • Katedra Genetyki Ogólnej, Biologii Molekularnej i Biotechnologii Roślin, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki, Banacha 12/16 90-237 Łódź, Polska
  • Department of General Genetics, and Plant Molecular Biology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
  • Katedra Genetyki Ogólnej, Biologii Molekularnej i Biotechnologii Roślin, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki, Banacha 12/16 90-237 Łódź, Polska
  • Department of General Genetics, and Plant Molecular Biology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
  • Katedra Genetyki Ogólnej, Biologii Molekularnej i Biotechnologii Roślin, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki, Banacha 12/16 90-237 Łódź, Polska
  • Department of General Genetics, and Plant Molecular Biology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
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