Chromosomal Aberrations

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Chromosomal Aberrations
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Chromosomes

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

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Karyotyping

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

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Chromosomal aberrationschanges in the
chromosomes (mutations)

• Variations in the chromosome number
• Aneuploidy
• Addition or loss of one or more chromosomes
• Trisomy (2N1), monosomy (2N-1)
• Polyploidy
• Addition of chromosome sets
• Triploidy (3N), tetraploidy (4N)

• Alterations in the chromosome structure
• Deletion loss of part of a chromosome
• Duplication segment of a chromosome is repeated
• Inversion part of a chromosome is oriented in
  the reverse of its usual direction
• Reciprocal translocation part of a chromosome
  breaks off and attaches to another,
  non-homologous chromosome

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Identify the type of alteration that has
occurred.
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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)

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• 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

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Down Syndrome and Maternal Age
Some studies also show the gene for Alzheimers
disease is found in Chromosome 21 there may be a
correlation with Down Syndrome
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• 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.

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• 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.

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• 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)

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• 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
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• 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.
  

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• 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.

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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

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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

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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)

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• Translocation The Philadelphia Chromosome
• between one chromosome 9 and one chromosome 22.
  This translocation is designated t(922).
• 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

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Reciprocal translocation ? t(922)

• 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.

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• Robertsonian Translocation
• Down Syndrome Carrier t(1421)
• 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

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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 1421 Robertsonian
translocation.