When Meiosis Goes Wrong

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When Meiosis Goes Wrong

• Still in Chapter 15

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When Meiosis Goes Wrong

• Errors during meiosis can lead to genetic
  abnormalities
• Chromosomes
• Lose a piece (deletion)
• Recombine with a non-homologous chromosome
  (translocation)
• Separate incorrectly during anaphase
• Cytokinesis might not happen
• We can test for certain genetic abnormalities by
  doing a Karyotype

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Karyotype of The Human Genome

• Mitotic (doubled) chromosomes taken from a white
  blood cell at metaphase
• 23 chromosome pairs 46 total

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• Chromosomes are arranged by
• size
• location of centromere
• Banding patterns also help identify chromosomes

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The 23 Chromosome Pairs of Homo sapiens

• Autosomes chromosomes 1-22
• Sex chromosomes X and/or Y
• Autosomes carry genes for all functions
• Sex genes carry mostly genes for sex determination

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Amniocentesis

• Performed no earlier than 16th week of
  pregnancy
• Fetal Cells used to make Karyotype to check for
  chromosome abnormalities
• Biochemical analysis of amniotic fluid can detect
  various biochemical disorders e.g. tay sachs
• -Turn around time fetal cells must be cultured
  for at least 10 days before they can be
  karyotyped!
• Risks involved? Increased rate (about 1) of
  spontaneous abortion.

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Chorionic Villi Sampling (CVS)

• Performed 8 to 10 weeks into pregnancy.
• Karyotype Using villi cells
• DNA analysis
• Biochemical tests can be done on tissue
• Turn around time
• Karyotype can be produced same day CVS is
  performed!
• Risks?
• Spontaneous apportion (slightly higher than with
  amnio.)
• Can lead to malformation of fingers and toes (in
  .3 of cases)

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Making a Karyotype
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Chromosome Abnormalities

• Changes in chromosome number
• Increases in entire chromosome sets (polyploidy)
• Reductions or increase in ONE chromosome
  (aneuploidy)
• Changes in chromosome structure
• Translocation/Chromosomal Breaks
• Deletions
• Fragile sites

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Changes in chromosome number

• 1. Polyploidy presence of additional sets of
  chromosomes
• Common in plants
• Lethal in most animals
• 2. Aneuploidy presence of extra chromosome or
  an absence of one
• a. Trisomy three bodies having one
  extra chromosome
• b. Monosomy missing a single chromosome

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Polyploidy and Aneuploidy in Fruit Flies
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Meiotic nondisjunction causes the gain or loss of
single chromosomes
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Aneuploidy Monosomy vs. Trisomy

• Monosomy results from fertilzation between one
  normal gamete one gamete that is missing a
  chromosome.
• In Humans Autsosomal Monosomy extremely serious!
  Embryo usually ceases development very early.
  (considered lethal)

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• Trisomy results from fertilization between one
  normal gamete one gamete that contains an extra
  chromosome.
• In Humans Autosomal Trisomy usually results in
  spontaneous abortion.
• The only autosomal trisomies seen in live births
  are trisomy 13, 18 and 21.
• Trisomosy 21 (Down Syndrome) is the only
  autosomal trisomy that allows survival until
  adult hood.

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Edwards Syndrome Trisomy 18
Infant with Edwards Syndrome
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Down Syndrome Trisomy 21

• 1 in 900 live births
• Distinctive physical appearance wide skull, flat
  in back. Skin fold in corner of eye, tongue
  furrowed protruding, abnormalities in finger
  and palm prints,
• Development Mental retardation (but large
  variations in mental ability), slow growth,
  developmental delays
• Health Impact 40 have heart defects, Prone to
  respiratory infection, High leukemia rate.

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Karyotype of a Down Syndrome Female
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• Prognosis today many Down syndrome children
  reach adulthood. However, not many survive past
  50.
• Risk Factor Maternal Age

Note in Trisomy 21 that has occurred as a
result Of nondisjunction, the nondisjunction was
maternal 94 of the time! (In other trisomies
nondisjunction maternal 93 of time.)
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Why Is Non-disjunction Usually Maternal?

• Older Mother has greater chance of
  non-disjunction. ..if woman is 40 at time of
  conception, approx. 40 years to complete prophase
  I
• Perhaps uterus of older mother less sensitive to
  abmormal fetus. So older mothers less likely to
  spontaneously abort abnormal fetus.
• Or perhaps a combination of these factors.

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Sex Chromosome Aneuploidy

• Sex Chromosome Aneuploidy is more common than
  Autosome Aneuploidy!
• In order to survive and develop embryo needs at
  least one X chromosome.
• In healthy females, one X chromosome will be
  inactivated in each somatic cell. The inactivated
  X chromosome is referred to as a Barr body.
• An individual who has an intact Y-chromosome
  will be male, regardless of the number of X
  chromosomes he possesses.
• In the absence of an intact Y chromosome an
  individual will be female.

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Turner Syndrome

• Female (45 total chromosomes, 1 sex chromosome
  (X))
• Only monosomy that is Not lethal
• Abnormalities dont develop normal at time of
  puberty, underdeveloped breasts, rudimentary
  ovaries
• Infertile do Not ovulate or menstruate
• Treatment Hormone supplements can help these
  women lead normal lives

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Klinefelter Syndrome

• Male,( 47 total chromosomes, 3 sex chromosomes
  XXY)
• May have some learning difficulties but usually
  not mentally retarded
• Affected male may not develop normally at puberty
• In severe cases rudimentary testes prostate
  gland, sparse facial and pubic hair, long arms
  and legs, breast development may occur
• Infertility
• (in mild cases man may not discover disorder
  until he experiences infertility)

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Klinefelter Syndrome Karyotype
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Changes in chromosome structure

• Errors during recombination (Meiosis I) can
  result in some chromosomal abnormalities.
• Chromosomal aberrations fall into three general
  categories
• Translocation/Chromosomal Breaks
• Deletion
• Fragile site

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Translocations

• Translocations
• Simple translocation Broken chromosome fragment
  becomes attached to a nonhomologous chromosome
• Reciprocal translocation Broken chromosome
  fragments become exchanged between nonhomologous
  chromosomes

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Human Evolution

• Chimpanzees, Orangutans, and Gorillas all have 48
  chromosomes
• Humans have 46
• One hypothesis about the evolution of humans from
  chimpanzees is a fusion of chimpanzee chromosomes
  2 that lead to human chromosomes 2.

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Chromosomal Breaks

• Chromosome Breaks
• Spontaneous breaks due to errors in DNA
  replication errors in crossing-over
• Environmental factors UV light, Radiation,
  Viruses, Chemicals
• Cri du Chat Caused by partial deletion of
  Chromosome 5
• Infants cry sound like a cat. Speech problems
  after infancy. ? abnormal glottis larynx

Normal, Cri du Chat, Cat
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Fragile Sites

• Fragile X Syndrome normally CGG is repeated 50
  times in fragile X, up to 1000 times
• Makes a very thin physical region of the
  chromosome.
• Results in range of mental retardation and
  behavioral problems
• Occurs in both sexes most females with fragile X
  are heterozygous