294
Anthology of Human Repetitive DNA
&
mRNA
(A)
n
(A)
n
(A)
n
(A)
n
(A)
n
(A)
n
e1
e1
mRNA
(a)
Duplication
(b)
Deletion
copy1
pol II
e1
e3
e2
i1
i2
e4
i4
pol II
e1
e3
e2
i1
i2
e4
i4
pol II
e1
i1
e4
i4
pol II
e1
e3
e2
i1
i2
e3
e2
i2
e4
i4
e4
e1
e1
e3
e2
e1
e3
e2
e1
e3
e2
e4
e3
e2
Premature stop codon
(NMD sensitive?)
Frameshift
Exon
Intron
Different reading
frame
Downstream to stop
(noncoding part)
TE
Recombination
copy1
copy2
copy2
e1
i1
Fig. 14
Recombinations between repetitive elements and human disease.
Figure shows classical recombination between two direct intragenic repeats,
producing (a) exons duplication; and (b) exon deletion. The effects are
similar to those described in Fig. 13.
are likely to be NMD-sensitive, and the
resulting phenotype will be manifested by
lack of the corresponding protein.
The prevalence of Alu-mediated rear-
rangements is overwhelming: 55 out of
the 61 genes in Table 10 are affected by
Alu-induced recombinations. Only three
genes with L1 homologous recombina-
tions have been reported so far, and only
one case is known for endogenous retro-
viruses (Table 10). One deletion and one
translocation were induced by nonhomol-
ogous Alu-L1 recombinations. The excess
of detected Alu recombinations is proba-
bly related to the Alu genomic distribution
and structure. A typical Alu is about 300 bp
long, and this size seems to be sufFcient
for efFcient homologous recombination
in mammalian cells, where the mini-
mal length requirement is around 150 bp.
Alus are by far the most frequent repeats
found in human genes. L1 and endoge-
nous retroviruses are underrepresented in
GC- and gene-rich regions and are often
truncated or rearranged. The rearrange-
ments disrupt the long sequence similarity
necessary for homologous recombination.
In summary, Alu elements frequently pro-
vide closely spaced, highly identical copies
prone to recombination in GC-rich and
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