Biology Reference
In-Depth Information
after the staining of metaphase chromosomes. Three main categories are now rec-
ognized: (i) a highly repetitive class including sequence families with >10
5
copies
per haploid genome, (ii) a middle repetitive sequence class (10
2
-10
5
copies), and
(iii) a low repetitive class whose members possess between two and 100 copies per
haploid genome. The different classes of highly repetitive satellite DNA (tandem
repeats) are briefly reviewed here together with
Alu
repeats and LINE (L1) ele-
ments, the two most abundant and best characterized of the interspersed middle
repetitive sequence families in the human genome.
Tandem repeats.
Tandemly repetitive DNA comprises satellite DNA, minisatel-
lite DNA and microsatellite DNA. Satellite DNA comprises the majority of hete-
rochromatin and is clustered in tandem arrays of up to several megabases (Mb) in
length. A number of different families [e.g. simple sequence (5-25 bp repeats),
alphoid (169 bp and 172 bp repeat),
Sau
3A (~68 bp repeat)] have been identified
(reviewed by Vogt, 1990) which are largely confined to the centromeres. One func-
tion of satellite DNA could be to maintain regions of late replication thereby
ensuring that the centromere is the last region to replicate on a chromosome
(Csink and Henikoff, 1998).
The hypervariable minisatellite sequences (about 10
4
copies/genome) share a
core consensus sequence [GGTGGGCAGARG] which is reminiscent of the
Escherichia coli
Chi element known to be a signal for generalized recombination
(Jeffreys, 1987). These minisatellites exhibit substantial copy number variability
in terms of the number of constituent repeat units and are often telomeric in
location (see section 1.1.1,
Telomeres
).
Microsatellite DNA families are simple sequence repeats, the most common
being (A)
n
/(T)
n
, (CA)
n
/(TG)
n
and (CT)
n
/(AG)
n
types (Beckmann and Weber, 1992;
Vogt
et al
., 1990). Minisatellites and microsatellites account for between 0.2% and
0.5% of the human genome, respectively and are widely scattered on many chro-
mosomes. Their high copy number variability and association with a considerable
number of different genes has meant that they provide a very valuable source of
highly informative markers for disease analysis and diagnosis (Bruford and
Wayne, 1993). Since their presence at specific homologous chromosomal locations
is often evolutionarily conserved in primates (Coote and Bruford, 1996; Crouau-
Roy
et al
., 1996; Morin
et al
., 1998), they may also be useful in both population
genetic and evolutionary studies.
More recently, a further type of tandemly reiterated DNA sequence has been
described (Gondo
et al
., 1998). The 4746 bp RS447 repeat sequence, quaintly
named 'megasatellite' DNA, is repeated between 50 and 70 times on chromosome
4p15. It is evolutionarily conserved among mammals, polymorphic in humans
and since it contains an open reading frame, it may encode a protein product.
Alu
sequences and other SINEs.
The
Alu
family of short interspersed repeated
elements (SINEs) is present in all primates. Up to 900 000 copies are thought to
exist in the human genome (some 5% of the total DNA complement) with an aver-
age spacing of 4 kb (Hwu
et al
., 1986). Most occur in noncoding DNA but some
are known to be located in untranslated regions (Makalowski
et al
., 1994) or even
coding regions (Margalit
et al
., 1994).
