Biology Reference
In-Depth Information
genomes is especially important because the mouse represents a genetic system
with a large number of spontaneous mutants (some of which are relevant to the
study of human genetic disease), numerous inbred strains and enormous poten-
tial for the application of transgenic technology (Rubin and Barsh, 1996).
The latest comparative genetic map for human and mouse contains nearly 1800
genes mapped to over 200 different syntenic chromosomal groups [DeBry and
Seldin, 1996;
http://www.ncbi.nlm.nih.gov/Homology/
]. Despite a timespan of
between 100 (Kumar and Hedges, 1998) and 80 Myrs (Collins and Jukes, 1994)
since the divergence of the two species, some syntenic groups have maintained
gene content, order and spacing over considerable genetic and physical distances,
for example the 1q21-q23 region of human and mouse chromosomes 1 (Oakey
et
al
., 1992) and a portion of mouse chromosome 2 with the entire human chromo-
some 20 (DeBry and Seldin, 1996). Other syntenic groups, by contrast, have accu-
mulated substantial differences in gene order between the two species, for
example human chromosome 19q13 and a segment of the homologous murine
chromosome 7 which exhibit nine separate conserved linkage groups (DeBry and
Seldin, 1996). The human and mouse X chromosomes contain a minimum of
eight conserved syntenic groups (Blair
et al
., 1994). The possible events which
may have led to the current arrangement of homologous segments on the human
and murine X chromosomes are shown in
Figure 2.2
and discussed further in
Section 2.3.4.
Syntenic regions need not, however, necessarily be comparable in size. Thus, the
human T-cell receptor
(
TCRB
; 7q35) region (800 kb in length) is considerably
larger than its murine counterpart (500 kb) as a result of repeated duplications of
specific V
segments in the primate lineage (Hood
et al
., 1993). Similarly, the
human HLA class II region (6p21.3) at ~900 kb is approximately three times the
length of its mouse equivalent as a result of the duplication of specific HLA-DP, -
DQ and -DR members of this multigene family in the primate lineage (Amadou
et
al
., 1995; Hanson and Trowsdale, 1991). By contrast, the class III HLA regions of
human and mice are remarkably similar in structure (Peelman
et al
., 1996).
Many syntenic blocks extend across human centromeres (Moseley and
Seldin, 1989). Thus, gene order in the pericentric regions of human chromo-
somes 1, 2, 4, 6, 11, and 19 is conserved in the homologous regions of murine
chromosomes 3, 6, 5, 1, 2, and 8, respectively (DeBry and Seldin, 1996). The
majority of rearrangements appear to be due to inversions within chromosomes
rather than rearrangements between chromosomes but more detailed mapping
data will be required to obtain the map resolution necessary for a definitive
assessment. One
caveat
which should be borne in mind is that the linkage map
may have been broken up to a larger extent in rodents than in primates as com-
pared to the ancestral mammalian genome (Lundin, 1993). One way to study
this type of rearrangement is by the comparative analysis of the chromosomal
locations of the individual gene loci involved. For example, Maresco
et al
. (1998)
determined the locations of the high-affinity immunoglobulin receptor genes
(
FCGR1A
, 1q21;
FCGR1B
, 1p12;
FCGR1C
, 1q21) in the rhesus monkey
(
Macaca mulatta
), baboon (
Papio papio
) and chimpanzee (
Pan troglodytes
) thereby
providing evidence for the occurrence of two pericentric inversions during the
evolution of human chromosome 1.
