CYTOGENETICS

CHROMOSOMAL ABNORMALITY

NORMAL CHROMOSOME STRUCTURE The chromosome parts that lie between

protein-rich areas and the telomeres are termed
● Mutations range from single-base
subtelomeres.
changes to entire extra sets of
chromosomes.
KARYOTYPE
● A mutation is considered a chromosomal Karyotype
aberration if it is large enough to z with a
● A karyotype displays chromosomes in
light (electron) microscope.
pairs by size and by physical landmarks
A chromosome consists primarily of DNA that appear during mitotic metaphase,
and proteins with a small amount of RNA, and is when DNA coils tightly.
duplicated and transmitted—via mitosis or
meiosis.

CENTROMERE POSITION
Euchromatin
➔ Lighter color, more protein-coding
sequences.

Heterochromatin
➔ Highly repetitive DNA sequences.

TELOMERES
Telomeres
● Chromosome tips. Each telomere has
many repeats of sequence TTAGG. Metacentric
● If the centromere divides into two arms
● Telomeres shorten with each mitotic cell of approximately equal length.
division
Submetacentric
● Are the determinants of our cell age and
● If the centromere establishes one long
survival.
arm and one short arm.
● Function: less understood, but thought to
Acrocentric
play a role in DNA repair and
melanogenesis. ● If it pinches off only a small amount of
material toward one end.
CENTROMERES
Telocentric
Centromeres
● The centromere is at one end, although
● Largest constriction of a chromosome telomere sequences are still at the tip.
and it is where spindle fibers attach when
the cell divides.

● A chromosome without a centromere is

no longer a chromosome.
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CHROMOSOMAL ABNORMALITY

ABNORMAL CHROMOSOME NUMBER EUPLOID

Euploid
A human karyotype is abnormal if the
number of chromosomes in a somatic cell is not ● A normal chromosome number is euploid,
46, or if individual chromosomes have extra, which means “good set.”
missing, or rearranged genetic material.
POLYPLOIDY
Abnormal chromosomes account for at
Polyploidy
least 50 percent of spontaneous abortions.
● A cell with extra sets of chromosomes
Organisms that are euploid have a ● Triploid: a cell with three copies of each
chromosome number that is an exact multiple of a chromosome.
chromosome set.

● Two-thirds of all triploids result from

fertilization of an oocyte by two sperm.

● One-thirds (1/3) The other cases arise from

formation of a diploid gamete, such as when
a normal haploid sperm fertilizes.

● 17% of spontaneous abortions.

● Infants rarely survive.
● Dies within a few days after birth due to
organ failure.

ANEUPLOIDY
Aneuploidy
● Cells missing a single chromosome or
having an extra one

● “Not a good set.”

● Most autosomal aneuploids (with a missing
or extra non-sex chromosome) are
spontaneously aborted.

● Those that survive have specific

syndromes, with symptoms depending
upon which chromosomes are missing or
extra.

● Common in aneuploidy: Mental

retardation

★ Monosomy - one chromosome absent.

★ Trisomy - one chromosome extra.
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CHROMOSOMAL ABNORMALITY

Why Is Mental Retardation Common In ● A cell can have a missing or extra

Aneuploidy? chromosome in 49 ways—an extra or
missing copy of each of the 22 autosomes,
● Mental retardation is common in aneuploidy
because development of the brain is so ● Plus the five abnormal types of sex
complex and of such long duration that chromosome combinations—Y, X, XXX,
nearly any chromosome-scale disruption XXY, and XYY.
affects genes whose protein products affect
the brain.

VARIATION IN CHROMOSOMAL STRUCTURE

● In general, chromosomes can break due

● The meiotic error that causes aneuploidy to ionizing radiation, physical stress, or
is called nondisjunction. chemical compounds.

● In nondisjunction, a chromosome pair fails ● When a break occurs in the chromosome

to separate at anaphase of either the first or before DNA replication, during the S
second meiotic division. phase of the cell cycle, the break itself is
replicated.

● Broken DNA can still join together in the

process called restitution.
● If broken ends are not brought together,
they can remain broken.

● But, if broken chromatid ends are brought

into apposition, they may rejoin in any of
several ways.
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CHROMOSOMAL ABNORMALITY

ABNORMAL CHROMOSOME STRUCTURE

● Structural chromosomal defects include

missing, extra, or inverted genetic material
within a chromosome or combined or
exchanged parts of nonhomologs
(translocations).

● The centric fragment migrates

normally during the division process
because it has a centromere.The
acentric fragment, however, is
soon lost.

2. Deletion
NON CENTROMERIC BREAKS
● The viable, centric part of the
Single Breaks chromosome has suffered a
1. Restitution deletion. After mitosis, the daughter
● Rejoining of the broken ends of a cell that receives the deletion
single chromosome. (no chromosome may show several
consequence to the break) effects.

● Deleted following a single strand

break,

● Pseudodominance: The recessive

allele shows itself in the
phenotype as if it were dominant.

3. Dicentric bridge
● Two centric fragments of a single
chromosome may join, forming a
two-centromere, or Dicentric
Chromosome.

★ Acentric fragment - without centromere.

★ Centric fragment - with a centromere.

● The ultimate fate of this bridge is

breakage as the spindle fibers pull
the centromeres to opposite poles.
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CHROMOSOMAL ABNORMALITY

Two Breaks (Same chromosome)

Two possible outcomes:
1. Reunion that omits an acentric fragment,
which is then lost. The centric piece is the
Deletion Chromosome.

2. Two breaks in the same chromosome can

also lead to inversion, in which the middle
section is reattached but in the Inverted
Configuration.

1. Deletion
2. Inversion
● Breakage and reunion of
fragments in the same
chromosome, but with wrong
orientation.

★ Paracentric - centromere is not included

in the inverted section.

Outcome after crossing-over:

● 1- Normal chromatid
● 1- Dicentric chromosome
A study of duplications of parts of
● 1- Inversion chromatid
chromosome 15 revealed that small duplications
● 1- Acentric fragment
do not affect the phenotype, but larger ones may.
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CHROMOSOMAL ABNORMALITY

★ Pericentric - the inverted section TRANSLOCATION

contains the centromere.
Two major types of translocations:
Outcome after crossing-over: 1. Robertsonian Translocation
● 1- Normal chromatid ● The short arms of two different
● 1- Abnormal: duplication acrocentric chromosomes break,
● 1- Inversion leaving sticky ends on the two long
● 1- Abnormal: duplication arms that join, forming a large
chromosome with two long arms.

Two Breaks (Nonhomologous chromosome)

● In 1 in 20 cases of Down syndrome,

a parent has a Robertsonian
The ends of two nonhomologous translocation between
chromosomes are translocated to each other in chromosome 21 and another,
a reciprocal translocation. usually chromosome 14.

CENTROMERIC BREAKS
1. Fission
2. Fusion

2. Reciprocal Translocation
● Two different chromosomes
exchange parts.
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CHROMOSOMAL ABNORMALITY

Isochromosomes
● A chromosome that has identical arms.
● This occurs when, during division, the
centromeres part in the wrong plane.

Ring Chromosomes
● Ring chromosomes may arise when
telomeres are lost, leaving sticky ends that
adhere.