Download Chromosomal Aberrations

Chromosomal
Aberrations
Chromosomes
• contain units of
heredity (genes)
• composed of
chromatin (DNA +
protein)
• organisms contain
a specific number
of chromosomes
Karyotyping
• determines the number
and structure of
chromosomes in the cell
nucleus
• can be used to detect
chromosomal
aberrations
Chromosomal aberrations
changes in the chromosomes (mutations)
A. Variations in the
chromosome number
Aneuploidy
• Addition or loss of one or
more chromosomes
• Trisomy (2N+1), monosomy
(2N-1)
B. Alterations in the
chromosome structure
Deletion
• loss of part of a chromosome
Duplication
• segment of a chromosome is repeated
Inversion
Polyploidy
• part of a chromosome is oriented in the
reverse of its usual direction
• Addition of chromosome sets
• Triploidy (3N), tetraploidy
(4N)
Reciprocal translocation
• part of a chromosome breaks off and
attaches to another, non-homologous
chromosome
Identify the type of alteration that has
occurred.
A
B C
D
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F
G
H
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B C
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F G
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P
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M N
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B C
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O
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M N
B C
O
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H
F G
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H
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D E
F G
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G H
F G
H
Aneuploidy in humans
Trisomies in Autosomes
Trisomy 21:
Down Syndrome (47, 21+)
Trisomy 18:
Edwards Syndrome (47, 18+)
Trisomy 13:
Patau Syndrome (47, 13+)
Aneuploidy of Sex
Chromosomes
Turner Syndrome (45, XO)
Klinefelter Syndrome (47, XXY)
Jacobs Syndrome (47, XYY)
Metafemale (47, XXX)
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
Down Syndrome and Maternal Age
Some studies also show
the gene for Alzheimer’s
disease is found in
Chromosome 21; there
may be a correlation with
Down Syndrome
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;
5-10% of affected children survive
beyond the first year of life.
• The high mortality rate is usually due to
the presence of cardiac and renal
malformations, feeding difficulties,
sepsis, and apnea caused by CNS
defects.
• Severe psychomotor and growth
retardation are invariably present for
those who survive beyond infancy.
Trisomy 13: Patau Syndrome
• 1/5000 live births
• Multiple abnormalities, many of which are not
compatible with more than a few months of
life.
• Almost half of the affected infants do not
survive beyond the first month, and about three
quarters die within 6 months.
• 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. Hernias and genital
abnormalities are common.
• Because of the severity of congenital defects,
life-sustaining procedures are generally not
attempted.
Monosomy X (45, XO): TURNER SYNDROME
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•
•
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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)
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 are more severe
in 49,XXXXY than in 48,XXXY.
• Mortality rate is not significantly higher than in
healthy individuals.
Adolescent male who has
female-type distribution of
pubic hair and underdeveloped
testes.
Adolescent male with gynecomastia
(slightly developed breasts)
Tall stature – thin build and disproportionately long
arms and legs
Jacobs / XYY Syndrome (47, XYY)
• 1/1000 births
• Affected individuals are usually very tall and
thin.
• Many experience severe acne during
adolescence.
• Additional symptoms may include antisocial
or behavioral problems and learning
disabilities.
• Intelligence is usually normal, although IQ,
on average, is 10 to 15 points lower than
siblings.
Metafemale / XXX Syndrome
• 7.4-15.6/10,000 female births or 3.6-7.5/10,000 births
• Fetal death rate is not notably higher than that for conceptions with normal
chromosomes
• The clinical features are subtle and can be variable.
• Often not identified in infancy.
• Minor birth defects include wide spaced eyes, wide spaced nipples,
abnormally-sized head (either small or wide).
• Typically have tall stature by adolescence and normal sexual development
and puberty, are fertile, and have no or minor mental retardation but often
have learning disabilities and may have problems with motor coordination.
• Approximately 90% of cases are of maternal origin and 10% of paternal
origin. Of the triple X syndrome cases of maternal origin, 70% result from
nondisjunction in meiosis I, which increases with maternal age.
Abnormal Chromosome Structure
DELETION – a portion of a
chromosome is lost during cell
division; the chromosome from
which the fragment originated will
now be missing certain genes
Cri-du-chat Syndrome
(deletion at 5p)
• Deletion at short arm (p) of
chromosome 5
Cri-du-chat Syndrome
• Between 1 in 20,000 and 1 in 50,000
babies are affected
• Infants with cri du chat syndrome
commonly have a distinctive cat-like
cry (malformation of larynx)
• They also have an extensive grouping
of abnormalities with severe mental
retardation being the most important.
• Small head, wide-set eyes, low birth
rate, slow growth
Abnormal Chromosome Structure
DUPLICATION
• the fragment that got cut off from one chromosome attaches to its
homologue, thus duplicating certain genes on it
INVERSION
• the fragment that got cut off from one chromosome is able to RE-ATTACH
to it, but in the reverse orientation
TRANSLOCATION
• the fragment that got cut off from one chromosome attaches to another,
non-homologous chromosome
• it may also be an exchange of fragments between two non-homologous
chromosomes (reciprocal translocation)
Translocation: The Philadelphia Chromosome
• between one chromosome 9 and one chromosome 22. This
translocation is designated t(9;22).
• It results in one chromosome 9 longer than normal and one
chromosome 22 shorter than normal. The latter is called the
Philadelphia chromosome and designated Ph1.
• causes chronic myelogenous leukemia
• chromosome abnormality not found in any nonleukemic white
blood cells, nor in any other cells of the patient's body
Reciprocal translocation  t(9;22)
•
•
The fusion of the two genes
(red and green dots) in the
Philadelphia chromosome is
what eventually causes the
leukemia.
This is because it forms a new
protein that causes
uncontrollable cell division of
cells in the bone marrow that
give rise to WBC.
Robertsonian Translocation:
Down Syndrome Carrier – t(14;21)
• A portion of, or an entire, chromosome 21 fuses with one chromosome #14.
• Individual is phenotypically normal, but could have children with Down
Syndrome (gametes may be produced that contain one # 21 and the
abnormal # 14 (fused with 21); if fertilized, these would lead to Down
Syndrome
Tyler is a newborn baby suspected of having Down syndrome. Chromosome analysis reveals
that he has three copies of chromosome 21, but the long arm of one chromosome 21 is
translocated onto the long arm of one chromosome 14 at the centromere. Because
chromosomes 14 and 21 are acrocentric chromosomes, Tyler is said to have a Robertsonian
translocation. Chromosome analysis reveals that Tyler's father, Josh, has normal chromosomes,
but Tyler's mother, Dawn, has 45 chromosomes, including a balanced 14;21 Robertsonian
translocation.