Anthology of Human Repetitive DNA
257
boundary is often extended to 10–13 bp.
Microsatellites are much more abundant
than minisatellites.
The distribution of microsatellites in
the human genome appears to be more
uniform than that of minisatellites, with
approximately one microsatellite for ev-
ery 6 kb of DNA. Almost one-third of all
potential microsatellites are simple runs
of A. Such runs are often introduced as
poly(A) tails of non-LTR retroposons, in
particular, of Alu repeats (Sect. 3.1.2.2).
Therefore, the abundance of (A)
n
may
not be directly comparable to the abun-
dance of other, spontaneously expanding,
microsatellites. Other highly abundant
microsatellites ranked in descending or-
der are (AC)
n
, (AAAN)
n
, (AAAAN)
n
,and
(AAN)
n
, including the complementary se-
quences. Many of these A-rich microsatel-
lites are also spin-offs of poly(A) tails of
non-LTR retroposons. Microsatellites com-
posed of (CAG/CTG)
n
and (CGG/CCG)
n
trinucleotide repeats are less abundant, but
nevertheless very important due to their
connection with human diseases (Sect. 4).
The variation patterns of microsatellites
and minisatellites appear to be very simi-
lar. In each case, the majority of variations
are due to differences in the number of
tandemly repeated units, not from muta-
tions of the individual units. Despite the
similarities between micro- and minisatel-
lites, there are several different underlying
mechanisms involved in their evolution.
Indeed, the traditional division of tandem
repeats into microsatellites and minisatel-
lites is based on early hypotheses about
mechanisms driving their expansion. For
microsatellites, ‘‘replication slippage’’ dur-
ing DNA replication was suggested, while
minisatellite expansion was thought to
result from unequal crossing-over. Nev-
ertheless, our current knowledge suggests
that processes driving SSR expansion are
more complex and range from polymerase
slippage and gap repair to DNA recom-
bination and gene conversion. Another
pathway of SSR expansion involves an ini-
tial comobilization of the microsatellite or
minisatellite with transposition of another
repeat, as in the case of poly(A) tails of
non-LTR retrotransposons (Sect. 3.1).
Loci containing micro- or minisatellites
produce a very large number of variant
alleles, and the sequence length polymor-
phism makes micro- and minisatellites
some of the most informative genomic
markers. The most widely used microsatel-
lites are the (CA/GT)
n
dinucleotide re-
peats. The variation at microsatellite loci
has been used in genetic linkage analysis
to establish the locations of disease genes
as well as in forensics, human population
genetics, and cancer genetics.
Many other kinds of simple repetitive se-
quences represent variable permutations
of a limited number of motifs, some-
times interspersed with unique sequences.
Such ‘‘composed’’ or ‘‘cryptically simple
repeats’’ occur up to ten times more of-
t
enint
h
eg
en
om
i
cDNAt
h
a
nina
n
y
equivalent random sequence. They result
from a systematic reshuffling of various
DNA fragments differing in length and se-
quence composition. Therefore, they are
of interest from the standpoint of genetic
variability. These repeats have not yet been
systematically classi±ed or explored.
2.2
Satellites and Telomeric Repeats
Typically, satellites are arrays of 10
3
–10
7
tandemly repeated units, or monomers,
predominantly located in the well-de±ned
chromosomal
regions,
such
as
cen-
tromeres and heterochromatin. Tradition-
ally, the term
satellites
was restricted
to centromere-speci±c repeats; however,
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