Chromosomal Aberrations

1. CHROMOSOMAL
ABERRATIONS

2. Chromosomes
• contain units of
heredity (genes)
• composed of
chromatin (DNA +
protein)
• organisms
contain a specific
number of
chromosomes

3. Karyotyping
• determines the number
and structure of
chromosomes in the
cell nucleus
• can be used to detect
chromosomal
aberrations

4. NON-DISJUNCTION
•Failure of chromosomes to separate
during anaphase of mitosis or meiosis.

5. A. Variations in the chromosome number
1. Aneuploidy
• Addition or loss of one or more
chromosomes
• Trisomy (2N+1), monosomy (2N-1)
2. Polyploidy
• Addition of chromosome sets
• Triploidy (3N), tetraploidy (4N)
Chromosomal aberrations
changes in the chromosomes (mutations)

6. B. Alterations in the chromosome
structure
1. Deletion – loss of part of a chromosome
2. Duplication – segment of a chromosome
is repeated
3. Inversion – part of a chromosome is
oriented in the reverse of its usual
direction
4. Reciprocal translocation – part of a
chromosome breaks off and attaches to
another, non-homologous chromosome

7. A B C D E F G
H
A B C E F G H
A B C D E F G
H
A B C B C D E F
G H
A B C D E F G
H
A D C B E F G
H
A B C D E F G
H
M N O P Q R A B P Q
R
M N O C D E F G
H
Identify the type of alteration that has
occurred.

8. SOMATIC MOSAICISM
• When some cells in an individual have a
mutant version of gene while other cells in
the same have a normal version of the
same gene.
• Hemophilia, blood clotting disorder

9. CANCER CELLS
•Cells that grow out of control.

10. Fig.12-14
S
G1
M checkpoint
G2
M
Control
system
G1 checkpoint
G2 checkpoint

11. TUMORS
• BENIGN (non-cancerous)
• Grow locally and do not spread.
• MALIGNANT (cancerous)
• have the ability to spread and invade other
tissues
• METASTASIS: the process whereby cancer
cells break free from a tumor and travel to and
invade other tissues in the body.

12. Aneuploidy in humans
• Trisomies in
Autosomes
1. Trisomy 21: Down
Syndrome (47, 21+)
2. Trisomy 18: Edwards
Syndrome (47, 18+)
3. Trisomy 13: Patau
Syndrome (47, 13+)
• Aneuploidy of Sex
Chromosomes
1. Turner Syndrome
(45, XO)
2. Klinefelter Syndrome
(47, XXY)

13. TRISOMY 21 (47, 21+): DOWN SYNDROME
• Most common single cause of birth defects in
humans
• 1/660 births
• Prominent facial features (upward slanting
eyes, open mouth with tongue protrusion)
• Simian crease in palm (one horizontal line
only)
• Mental retardation that ranges from mild to
severe
• Congenital heart defects
• Increased susceptibility to many diseases
• Mostly sterile
• Shorter life span
• Increased risk with older mothers

14. Trisomy 18: Edwards Syndrome
• Second most common autosomal
trisomy after trisomy 21.
• 1/6000-8000 live births
• Severely affects ALL organ
systems
• Approximately 95% of
conceptions with trisomy 18 die in
embryonic or fetal life;
• The high mortality rate is usually
due to the presence of cardiac
and renal malformations, feeding
difficulties.
• Severe psychomotor and growth
retardation are invariably present
for those who survive beyond
infancy.

15. TRISOMY 13: PATAU SYNDROME
• 1/5000 live births
• Multiple abnormalities, many of which
are not compatible with more than a few
months of life.
• Severe mental defects and defects of
the brain that lead to seizures, apnea,
deafness, and eye abnormalities.
• Most infants have a cleft lip and cleft
palate, polydactyly and low-set ears.
• Congenital heart disease is present in
approximately 80% of affected infants.
• Because of the severity of congenital
defects, life-sustaining procedures are
generally not attempted.

16. MONOSOMY X (45, XO): TURNER SYNDROME
 The only known viable monosomy in humans
 1/2000 live female births (and 15% of spontaneous
abortions)
 Phenotypically female
 Sterile, short stature, webbed neck, immature sex
organs, secondary sexual characteristics fail to develop,
“shield”-type chest (broad and flat)

17. Klinefelter Syndrome: 47, XXY
• Approximately 1 in 500-1,000 males
is born with an extra sex
chromosome;
• About 40% of conceptions with
Klinefelter syndrome survive the fetal
period.
• In general, severity of somatic
malformations in Klinefelter
syndrome is proportional to the
number of additional X
chromosomes; mental retardation
and hypogonadism
• Mortality rate is not significantly
higher than in healthy individuals.
Tall stature – thin build and disproportionately long
arms and legs