Biology Reference
In-Depth Information
sequences and their variants are tandemly repeated but are nonrandomly distrib-
uted and polymorphic in terms of their location. Chimpanzees also possess the
TTAGGG telomeric repeat (Luke and Verma, 1993) but differ from humans in
terms of their subterminal satellite sequences (Royle
et al
., 1994).
The simple sequence of telomeres is synthesized by the ribonucleoprotein poly-
merase,
telomerase
(Blackburn, 1992), and is thought to protect the ends of chromo-
somes from degradation during DNA replication. Telomere length decreases with
age and number of cell divisions. Some chromosomes (e.g. 9p, 12p, 14p, 17p, 21p
and 9q) have telomeres shorter than the average whereas others (e.g. 4q, 5p, 18q and
Xp) have telomeres which are longer (Martens
et al
., 1998). Telomere length poly-
morphisms are apparent for some chromosomes, for example 11p (Martens
et al
.,
1998).
Sites of recombination.
Chiasmata represent the cytological evidence for
recombination. At meiosis, each pair of homologous chromosomes possesses at
least one chiasma and the number of chiasma per pair is proportional to the size
of the chromosome. Chiasma frequency is a function both of distance from the
centromere (Laurie and Hulten, 1985) and chromosome band 'flavor': the G+C
rich T bands exhibit a six-fold higher chiasma frequency than G bands
(Holmquist, 1992). Since G+C content is in general positively correlated to chi-
asma frequency (Eyre-Walker, 1993), this could explain why gene density is
higher in T bands (see section 1.1.1,
Gene distribution and density
).
Recombination is considerably higher in human females than in males, as evi-
denced by the average distance between two markers in the female genetic map
being 85% longer than in males. Chiasma frequency is a function of distance from
the centromere (Laurie and Hulten, 1985). Recombination therefore tends to
increase towards the telomeres, the distal 15% of chromosomes containing 40% of
the chiasmata. Finally, it may also be pertinent to consider that intrachromosomal
homologous recombination may be enhanced by transcription in mammalian
cells (Nickoloff, 1992).
Obligatory recombination occurs during male meiosis within the pseudoauto-
somal region, a 2.6 Mb stretch of homologous sequence at the tip of the short arms
of the X and Y chromosomes (Petit
et al
., 1988; Ellis and Goodfellow, 1989). Genes
in this region escape X-inactivation and the boundaries of this region appear to
have been conserved evolutionarily between Old World monkeys and human
(Ellis
et al
., 1990).
Regions of sex-specific hypo- and hyper-recombination have been reported in a
study which compared genetic and physical maps of human chromosome 19
(Mohrenweiser
et al
., 1998). Other recombination hotspots have been character-
ized in specific human genes including those encoding the T-cell receptor beta
chain (
TCRB
; 7q35; Seboun
et al
., 1993) and HLA-associated ATP transporter 2
(
TAP2
; 6p21.3; Cullen
et al
., 1995) loci. Several different types of DNA sequence
have been proposed to be recombinational hotspots in the genomes of mice and
men. (CAGA)
6
and (CAGG)
7-9
represent hotspots of recombination in the murine
MHC gene cluster (Steinmetz, 1987). Other sequences thought to promote recom-
binational instability are alphoid repeats (Heartline
et al
., 1988), a
mariner
transpo-
son-like element (Reiter
et al
., 1996), Z-DNA ('left-handed DNA'; Wahls
et al
.,
