Biology Reference
In-Depth Information
FIGURE 2.2. (A) Structural chromosomal abnormalities may lead to translocations,
inversions, or deletions. (B) A paracentric inversion on mouse chromosome 9 leads
to the
se
sv
combined phenotype of short ear (
se
) and Snell's waltzer (
sv
, deafness
and circling) (Avraham et al. 1995). Breaks occur at the dotted lines, causing the
myosin VI (
Myo6
) gene, normally transcribed in the direction shown by the arrow,
to be inverted. Upstream regulatory regions, shown in grey, are lost, leading to
down-regulation of myosin VI expression.
waltzer (
Myo6
) genes (Fig. 2.2B). No other genes appear to be affected,
since the inverted DNA remains intact (except for small deletions at each
breakpoint) and the mice only harbor phenotypes representative of the two
genes. The breakpoints near the
Bmp5
and
Myo6
genes affect the down-
stream and upstream regions of these genes, respectively, leading to skele-
tal (for
Bmp5
; DiLeone 1998) and hearing (for
Myo6
) abnormalities in
these mice. The consequence of this inversion is a position effect, where the
expression of a gene is altered due to the relocation of chromosomal
regions.
Most chromosomal deletions causing NSHL are intragenic (within the
gene) and comprise no more than a few base pairs. One exception is the X-
linked
DFN3
locus, with mutations in the
POU3F4
gene. Several chromo-
