Translocation

Translocation refers to an exchange of chromosome
segments. A translocation can arise by
centric fusion of two acrocentric chromosomes
(Robertsonian translocation) or by exchange
between two chromosomes (reciprocal translocation).
With centric fusion, two complete chromosomes
are involved; with reciprocal translocation,
only a part of each of the two chromosomes
is exchanged. In a translocation it is important
to determine the breakpoints in each of
the chromosomes involved.

Centric fusion of acrocentric chromosomes

Chromosome 14 and chromosome 21 (1) are the
most frequently involved in fusions (about 1 in
1000 newborns). By fusion of the long arm of
chromosome 21 (21q) and the long arm of chromosome
14 (14q), a chromosome t (14q21q) is
formed (2). The satellite-carrying short arms of
both chromosomes are lost, but this is insignificant.
When germ cells (gametes) are formed,
deviation from the normal chromosome number
may result (3). Since chromosome 14 and
chromosome 21 pair during meiosis, the following
possible gametes may result: chromosome
14 alone (no chromosome 21), one chromosome
14 and one chromosome 21 (normal),
the chromosome 14 fused to chromosome 21
(balanced), or the fused chromosome and one
chromosome 21

After fertilization

After fertilization, the corresponding zygotes
contain either only one chromosome 21 (unviable
monosomy 21), a normal chromosome complement,
a balanced chromosome complement
with the fused chromosome, or three chromosomes
21 (trisomy 21). In the latter case, the
clinical disorder Down syndrome (formerly
called mongolism) results

Reciprocal translocation

A reciprocal translocation is an exchange of
chromosomal material between two chromosomes.
Since usually no chromosomal material
is lost or added with a reciprocal translocation,
it does not cause clinical signs (i. e., it is
balanced). However, carriers of a reciprocal
translocation may form gametes with unbalanced
chromosome complements. During
meiosis, the chromosomes involved in the reciprocal
translocation take part as usual in the
homologous pairing of meiosis I. Each of the
chromosomes not involved in the translocation
pairs with its homologous partner that is involved
in the translocation. This leads to the formation
of a characteristic quadriradial configuration
of the involved chromosomes. When
these four chromosomes separate (segregation)
during anaphase of meiosis (see p. 116), one of
three possibilities may occur: With alternate
segregation, one gamete receives the two normal
chromosomes, and the other gamete the
chromosomes involved in the translocation,
i. e., it is balanced.

.......

With nonalternate segregation (neighboring or
adjacent chromosomes), the two chromosomes
on the left go into one gamete and the two chromosomes
on the right into the other (adjacent-
2). With the other possibility, the upper chromosomes
go into one gamete, and the lower
two into the other (adjacent-1). In each of the
last two cases, an unbalanced distribution of
the involved chromosome segments results. For
example, after adjacent-2 segregation, gametes
receive a partial duplication of the chromosome
segment marked with red and a partial deficiency
of the segment marked with blue (left
pair of chromosomes) or a partial duplication of
the blue segment and a partial deficiency of the
red (duplication/deficiency). Different types of
disorders result depending on the chromosome
segments involved.

Different Types of Structural Chromosomal Aberrations

Structural changes in chromosomes can be
classified according to cytological types and
their effect on the phenotype. The main cytological
types are translocation (exchange) (see
p. 198), deletion (loss, see p. 182), inversion, insertion,
isochromosome, dicentric chromosome,
and ring chromosome (see below). According
to their effects, they can be differentiated
as balanced or unbalanced. With a
balanced rearrangement, no chromosomal
material has been lost or gained. In this case,
there is no effect on the phenotype. In unbalanced
aberrations, chromosomal material
has either been added (partial duplication) or
lost (partial deficiency).

Inversion

An inversion is a 180-degree change in direction
of a chromosomal segment. Prerequisite for
every inversion is a break at two different sites,
followed by reunion of the inverted segment.
Depending on whether the centromere is involved,
a pericentric inversion (when the
centromere lies within the inverted segment)
and a paracentric inversion can be differentiated.