Biomedical Engineering Reference
In-Depth Information
7.5
Types of mutations that can occur
at the chromosomal level
By some estimates 50% of all conceptions have a chromosome abnormality.
However, by the time of birth, the fi lter of gestation results in only about
0.67% of live born infants with a detectable chromosome abnormality.
About 15% of diagnosed pregnancies result in spontaneous abortions and
about half of these show a chromosome anomaly. Some 6% of stillborns and
6% of neonatal deaths are chromosomally abnormal. Fetuses with chro-
mosome abnormalities tend to be small, have multiple malformations, and
hydrops fetalis. Infants that are small or dysmorphic should be karyotyped.
Moreover, couples that have experienced multiple reproductive losses
should be karyotyped to determine if one of them is a balanced carrier for
a chromosome rearrangement that results in unbalanced gametes. There
are two basic types of chromosome abnormalities:
numerical
and
structural
.
These are discussed in the following sections.
7.5.1 Numerical abnormalities
Numerical abnormalities are numerical changes to the normal diploid chro-
mosome number and result in (i) aneuploidy, where there is the addition or
loss of a chromosome called trisomies and monosomies and (ii) polyploidy
where there is the addition of a complete haploid set of chromosomes to the
cells of the individual.
The primary mutational event that leads to these numerical chromosomal
changes resulting in trisomies and monosomies is called nondisjunction
(Fig. 7.12). This process is the failure of the chromosomes or chromatids to
segregate normally into daughter cells during either meiosis or mitosis. If
the mitotic nondisjunctional event happens during early cleavage, the resul-
tant individual will be a mosaic with more than one cell line contributing to
the phenotype (chromosomal mosaicism). Meiotic nondisjunction can hap-
pen in either the fi rst or second division or results in gametes which can
potentially produce either trisomic or monosomic offspring. Some impor-
tant things to remember about nondisjunction are:
Nondisjunction seems to occur more often in oogenesis than during
spermatogenesis.
The extra chromosome seen in Down syndrome patients is of maternal
origin more than 75% of the time (with some studies revealing as high
as 90%).
There is no proven genetic etiology for nondisjunction in humans.
There is a clear infl uence on the rate of nondisjunction, which increases
with maternal age.
