attached to each other at the CENTROMEREuntil cell
division. When the mother cell divides, the sister
chromatids separate at the centromere and
migrate into the new daughter cells, forming the
chromosome pairs for the new cells. Though
minor variations are normal and frequently occur
without causing problems because they affect rela-
tively few cells, errors in chromatid replication
and separation affect many or all cells and can be
responsible for CHROMOSOMAL DISORDERS such as
DOWN SYNDROME.
For further discussion of chromatids within the
context of the structures and functions of genetics,
please see the overview section “Genetics and
Molecular Medicine.”
See also CELL STRUCTURE AND FUNCTION; DNA;
GENETIC DISORDERS; MOSAICISM; MUTATION; NUCLEOTIDE;
VARIATION.
chromosomal disorders Abnormalities affecting
the chromosomes that result in syndromes (con-
stellations of symptoms) having characteristic
physical or functional anomalies. Most chromoso-
mal disorders occur because of alterations in the
number of chromosomes or the structure of chro-
mosomes. Though an individual may inherit a
chromosomal disorder, more commonly chromo-
somal disorders represent random occurrences.
Typically all the cells in the body reflect the abnor-
mality. Occasionally some but not all cells carry
the chromosomal abnormality; this is a mosaic
chromosomal disorder. A mosaic presentation
tends to be milder than that observed when all
cells carry the chromosomal abnormality
Disorders of ReplicationNormally chromosomes exist in pairs. Replication
errors can result in an incorrect number of chro-
mosomes passing to new cells. Though such errors
can occur in any cell with any episode of cell divi-
sion, they are most harmful when they affect
gametes (the sex cells, the ovum in the female and
the spermatozoon in the male). Replication errors
in gametes become chromosomal disorders in the
new life created through their union. These errors
may take the form of trisomy (an extra CHROMO-
SOME), monosomy (a missing chromosome), or
uniparental disomy (both copies of a chromosome
come from the same GAMETEor parent).
Trisomy Disorders of trisomy occurs when the
ZYGOTEreceives three instead of the normal two
copies of a chromosome. Most trisomies are auto-
somal, and most autosomal trisomies are lethal
very early in embryonic development. Most early
losses due to trisomy thus likely escape detection.
The survivable autosomal trisomies affect chromo-
some 13 (PATAU’S SYNDROME), chromosome 18
(EDWARDS SYNDROME), and chromosome 21 (DOWN
SYNDROME). Trisomies can also involve the sex
chromosomes. The most common such disorder is
KLINEFELTER’S SYNDROME, in which the zygote
receives two (and sometimes more) X chromo-
somes and one Y chromosome. Though the Y
chromosome determines the gender as male, the
additional X chromosome affects sexual develop-
ment and FERTILITY. The zygote may also receive
three X chromosomes (triple X syndrome) or one
X chromosome and two Y chromosomes. These
trisomies may not produce obvious symptoms,
though often boys who have XYY syndrome have
developmental delays and learning disabilities.
MonosomyMonosomy occurs when the zygote
receives only one copy of a chromosome and
overall occur far less frequently than trisomy
because an entire missing autosome (nonsex chro-
mosome) is nearly always lethal. The monosomy
disorder Turner syndrome, in which the zygote
receives only one X SEX CHROMOSOME, is one of the
few survivable monosomy disorders. Because the
single sex chromosome is X, the zygote is female
although breast development at sexual maturity is
diminished.
Uniparental disomy In uniparental disomy the
zygote receives two copies of a chromosome from
one gamete and none from the other gamete.
Though in many cases this REPLICATION ERRORmay
result in no adverse symptoms or consequences, it
can allow rare recessive disorders to manifest.
Uniparental disomy also causes symptoms when
the involved chromosome is one in which GENETIC
IMPRINTINGis essential. In such circumstances the
chromosome pairing requires one chromosome
from each parent to activate the chromosome’s
genetic functions.Disorders of Structure
Chromosomal disorders of structure occur when
there are physical changes to the chromosomechromosomal disorders 117