The Principles of Clinical Cytogenetics - Extra Materials - Springer

186 Kathleen Kaiser-Rogers and Kathleen Rao
Fig. 13. A pseudoisodicentric chromosome involving the entire short arm and a portion of the long arm of
chromosome 9. It appears to have one constricted active centromere (upper dot) and one unconstricted inactive
centromere (lower dot). This chromosome was found in each of the cells of a phenotypically abnormal infant
with the following karyotype: 47,XY,+psu idic(9)(q21.1).
ACENTRIC CHROMOSOMES
Because the centromere is essential for chromosomal attachment to the spindle and proper segregation,
chromosomes lacking this critical component are rapidly lost. Therefore, although single
cells with acentric chromosomes or fragments are occasionally observed, individuals with constitutional
karyotypes that include a true acentric chromosome are never seen. More than 50 chromosomes
with atypical centromeres have, however, been reported in the literature (74). These atypical
centromeres or neocentromeres have now been reported in association with at least 18 different
chromosomes. Although clearly functional, the high incidence of mosaicism associated with
neocentromere-containing chromosomes suggests that these centromeres often do not function as
well as their normal counterparts.
Like traditional centromeres, neocentromeres are denoted by the presence of a primary constriction.
Interestingly, however, neocentromeres are located in noncentromeric regions and they interact
with only a subset of the centromeric proteins that typically bind active centromeres. Furthermore,
they do not react to stains specific for centromeric heterochromatin, nor do they hybridize to centromere
specific FISH probes. These staining differences suggested early on that the composition
of these neocentromeres differed from that of a traditional centromere. Subsequent mapping and
sequencing studies have since confirmed this. Current data suggest that neocentromeres do not contain
DNA sequences that we typically associate with centromeres, such as α-satellite DNA. In fact,
the DNA sequence within such an atypical centromere does not appear to be altered relative to the
homologous region of the parental chromosome from which it was derived (75). These data, in addition
to DNA modeling studies, suggest that it is the conformation or secondary structure formed by
the DNA, rather than the DNA sequence itself, that enables a chromosomal region to function as a
neocentromere. It has been speculated that neocentromeres might represent ancient centromere
sequences that have been reactivated as a consequence of chromosome rearrangement (76,77).
ISOCHROMOSOMES
An isochromosome consists of two copies of the same chromosome arm joined through a single
centromere in such a way that the arms form mirror images of one another. Individuals with 46
chromosomes, 1 of which is an isochromosome, are monosomic for the genes within the lost arm and
trisomic for all genes present on the isochromosome. Tetrasomy for the involved chromosome segment
is present when an isochromosome is present as an extra (supernumerary) chromosome. In
general, the smaller the isochromosome, the smaller the imbalance and the more likely the survival of
the fetus or child that carries the isochromosome. It is therefore not surprising that, with few exceptions,
the most frequently reported autosomal isochromosomes tend to involve chromosomes with