Anthology of Human Repetitive DNA
283
provirus was inserted into an active Rick-
sha
0 copy, which amplifed into the
Ricksha subFamily. A second Family oF hu-
man MuDR-like transposons was reported
recently as the Merlin1
HS autonomous
transposon, which encodes a transposase
that is the most similar to the IS1016
bacterial transposase. Since the IS1016
and IS256 transposases are distantly re-
lated, Merlin1
HS can be considered to
be a member oF the MuDR superFam-
ily, quite diFFerent From standard MuDR
transposons. Merlin1
HS is characterized
by the 8-bp TSDs and 21-bp TIRs with
5
0
-GGA and TCC-3
0
termini. The human
genome harbors Fewer than 100 copies
oF Merlin1
HS. They are
20% diver-
gent From the consensus sequence, which
indicates their activity some 100 million
years ago.
4
Repetitive Elements and Human Diseases
The potential pathogenic impact oF repet-
itive elements can maniFest itselF through
a broad spectrum oF pathways. The frst
category oF disorders is linked to the
expression oF active TEs, particularly to
the production oF proteins. Such proteins
can interFere with cellular processes and,
most importantly, they can provoke host
immune reactions against cells contain-
ing TE antigens. The second group oF
pathogenic eFFects linked to repetitive DNA
includes mutations and genetic rearrange-
ments such as satellite expansion, repeat
insertions, deletions, illegitimate recombi-
nation, or nucleolytic activity oF proteins
encoded by TEs. These mutations can oc-
curbothingermlineorsomaticcells.
The pathogenic potential oF TE-derived
protein products is Far From being un-
derstood. Relevant research was done
mostly
on
human
endogenous
retro-
viruses (HERVs; Sect. 3.1.2). HERVs have
been proposed as causative agents oF
autoimmune diseases such as rheuma-
toid arthritis, systemic lupus erytremato-
sus,
insulin-dependent
diabetes
melli-
tus, and multiple sclerosis. Other po-
tentially HERV-linked disorders include
schizophrenia and several types oF cancer.
In many such cases, retroviral mRNAs
or even entire particles were detected
in malignant tissues. Retroviral antigens
such as the
gag
gene product may indeed
trigger immune reaction against aFFected
tissues leading to autoimmune abnormal-
ities. However, it is still unclear whether
expression oF retroviral mRNAs and pro-
teins causes or merely correlates with the
pathological processes. Increased expres-
sion oF TEs is typical oF many cellular
alterations including cell transFormations.
This indicates that rather than inducing
the pathogenesis, the expression oF TEs
may simply reflect relaxed transcription
control in malignant cells.
Repeat-induced DNA rearrangements
represent a wide range oF mutation deFects
related to the amplifcation oF repetitive ele-
ments and genetic recombination. Genetic
diseases can be caused by both simple and
interspersed repeats. The unstable expan-
sions oF simple sequence repeats, namely,
trinucleotides, are involved in a number
oF genetic diseases. The Fragile X syn-
dromes (known as ±RAXA and ±RAXE)
involve CGG and GGC triplet expansions.
Myotonic dystrophy can be caused by the
CTG/CAG repeat expansion. Other exam-
ples oF diseases associated with moderate
expansion oF CAG repeats include neural
diseases such as Kennedy’s disease, Hunt-
ington’s disease, spinocerebellar ataxia 1
(SCA1) and dentatorubropallidoluysian at-
rophy (DRPLA). The disease-related triplet
expansions are much more Frequent than
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