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variation due to TE presence or absence and as a consequence, considerable
interindividual variation in the combined TE activity. These observations com-
bined with the significant tissue-specific variation in the endogenous L1 expres-
sion in somatic human tissues (Belancio
, 2010b) suggest that TE-associated
genetic variation is likely to exist among somatic tissues of the same individual.
et al.
IV. GENOMIC INSTABILITY
One of the main conflicts between TEs and their host genomes arises from the
fact that multiple aspects of TE activity pose a challenge to the structural
integrity of the genome. These include L1-iduced DSBs, L1, Alu, and SVA
retrotransposition and retrotransposition-mediated rearrangements (deletions,
insertions, inversions; Gilbert
, 1999; Ostertag
and Kazazian, 2001), and TE-associated recombination [reviewed in Hedges and
Deininger, 2007](Fig. 6.2).
et al.
, 2002, 2005; Moran
et al.
Retrotransposition
Non-Allelic
Homologous
Recombination
DNA double
strand breaks
Gross genomic rearrangements
Gross genomic rearrangements
Senescence-like phenotype
Senescence-like phenotype
Figure 6.2. L1-associated genomic instability. Human non-LTR transposable elements can trigger a
number of events leading to mutagenic alterations in the host genome. Among them are
retrotransposition, DNA double-strand breaks (DSBs), and nonallelic homologous re-
combination (NAHR). Out of the three human non-LTR TEs only L1 elements can
induce all of these events. L1, Alu, and SVA retrotransposition causes insertional
mutagenesis when the
integrations reside within or near human genes or
functional regulatory elements. Both retrotransposition and NAHR lead to interference
with normal gene expression through alterations in the gene regulation and/or proces-
sing. NAHR and L1-associated DSBs have a potential to produce gross genomic rear-
rangements. In addition, L1-induced DSBs are reported to induce cell-cycle arrest,
apoptosis, and senescence-like phenotype in normal and cancer cells.
de novo
