Anthology of Human Repetitive DNA
gene-rich regions, and thus represent the
main risk for human genetic disorders
caused by recombination between repeti-
tive elements.
Alu sequences contain several regions
with elevated occurrence of recombination
breakpoints. These include promoters and
the AT-rich linker between the left and
right Alu monomer. Moreover, Alu el-
ements harbor a 26-bp motif (positions
22–47 at the Alu consensus), possibly
associated with increased frequency of
recombination. The region contains the
pentanucleotide motif core CCAGC, which
is also part of chi, and an 8-bp sequence
known to stimulate recBC-mediated re-
combination in
Escherichia coli
Alu repeats have also been implicated
in the etiology of some recurrent so-
matic chromosome rearrangements de-
tected in neoplastic tissues. The large-
karyotype changes such as Philadelphia
translocation, which is associated with
chronic myelogenous leukemia. Chromo-
somal aberrations found in cancers result
in loss of heterozygosity and in cancer
progression. Apart from somatic translo-
cation, nonlethal cytogenetically balanced
chromosomal translocations in germline
cells can lead to constitutional congenital
disorders. An Alu-mediated translocation,
t(9;11)(p23;q23), was shown to cause a fa-
milial form of the bipolar affective disorder
(manic depression). Also, a patient with
translocation t(1;19)(q21.3;q13.2) induced
by nonhomologous Alu-L1 recombination
was diagnosed with brain atrophy, ataxia,
and mental retardation.
against deleterious changes. For example,
the reciprocal translocation t(11;22)(q24;
q12) fusing the Ewing’s sarcoma (EWS)
gene on 22q.12 with the
gene on
11q.24, is associated with about 80%
of primitive neuroectodermal tumors, in-
cluding Ewing’s sarcoma. However, a
2.4 kb Alu-mediated deletion in ESW in-
tron 6, located near the translocation
hotspot, seems to stabilize the region,
since the carriers of this allele have a ten-
fold decreased incidence of EWS compared
to populations without the 2.4 kb deletion.
In summary, repetitive elements con-
tribute to human diseases through a
variety of mechanisms. While the patho-
genetic effects of repeat-encoded mRNAs
and proteins are still debatable, repeat
insertions and recombinations are sig-
ni±cant contributors to genetic variability
and abnormalities. The overall frequency
of such events is unknown. Typical PCR-
based detection of human mutations fails
to amplify many large-scale variations,
and the resulting defects are likely to be
underrepresented in mutation databases.
Also, germline recombination producing
large rearrangements can terminate em-
bryonic development in early stages, thus
providing no opportunity for prenatal
The impact of retrotransposon inser-
tions is small compared with the effect
of deletions. Insertions correspond to
about 0.1% of all human diseases. Alu-
mediated recombinations are estimated
to contribute to only 0.3% of human
diseases. However, since large rearrange-
ments (about 7.4% of all human muta-
tions) often lack precise determination of
breakpoints, it is possible that the impact
of Alu recombination is higher.
Potential Contribution of Repetitive DNA to
Cellular Functions
volved in a broad variety of processes
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