Biology Reference
In-Depth Information
of 146 DNA nucleotides to form an 11 nm nucleosome (1 nm is a billionth
of a meter). The nucleosomes, like beads on a string, further wind around
each other to create the 30 nm chromatin fibers (Fig. 2.1). This compaction
is necessary, since the human haploid genome, if stretched out, would reach
the height of a person. A copy of this genome is present in each cell.
2.1 Chromosomal Abnormalities Leading to Deafness
Chromosome abnormalities can either be numerical or structural in nature,
and usually lead to extreme phenotypes (Table 2.1). They often affect a
large genomic DNA region, and can result in the loss or gain of partial or
whole chromosomes. Large chromosome abnormalities can lead to embry-
onic lethality from the loss of one or more essential genes, or to a disease
with several phenotypes, as is seen with syndromic hearing loss. The most
common chromosome abnormalities are numerical and involve the loss or
gain of whole chromosomes. Polyploidy, which describes the presence of an
extra copy of the entire set of chromosomes, is not viable in humans. In con-
trast, some forms of aneuploidy (the loss or gain of one chromosome) are
compatible with life (Giersch and Morton, Chapter 3). The most common
form is the gain of an additional chromosome 21 (trisomy 21), which leads
to Down syndrome. Some trisomy 21 patients exhibit conductive and/or
sensorineural hearing loss, although the gene(s) contributing to the hearing
loss are unknown (Gorlin et al. 1995).
Structural chromosomal abnormalities involve chromosome breaks, with
rejoining of breakpoints in several possible configurations. The breaks
may affect one or more genes, and lead to chromosomal translocations,
inversions and deletions (Fig. 2.2A). When a translocation occurs, genetic
material is transferred from one chromosome to another. An inversion is a
reversal in the order of a chromosomal segment; genetic information is
usually not lost, but the linear sequence of the genes is altered. A pericen-
tric inversion involves the centromere, whereas a paracentric inversion does
not include the centromere. Although chromosome breaks are uncommon
in nonsyndromic sensorineural hearing loss (NSHL), a paracentric inver-
sion is known to cause NSHL in the mutant deaf mouse, Snell's waltzer
(Avraham et al. 1995). The chromosomal breakpoints of this inversion are
near, but not within, the coding regions of the short ear (
Bmp5
) and Snell's
TABLE 2.1. Types of chromosomal mutations
Chromosomal Abnormalities
Consequence
Numerical
Aneuploidy
Polyploidy
Structural
Translocations
Deletions
Inversions
