The nucleus: A review

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The nucleus A review
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• Meiosis
• Always results in formation of gametes
• Essentially just 2 phases of mitosis

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Normal Chromosome 21 gametogenesis
Sister chromatids of chromosome 21
4 copies
Meiosis I
2 copies
Meiosis II
1 copy
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1 copy each of chromosome 21
EGG
SPERM
2 copies of chromosome 21
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Downs Syndrome Trisomy 21
4 copies
Chromosome 21
Meiosis I nondisjunction
0 copies
4 copies
2 copies each
0 copies each
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Downs Syndrome
1 copy
2 copies
EGG
SPERM
88 of time maternal gamete is 2n for chromosome
21 8 of time paternal gamete is 2n for
chromosome 21 4 other
Trisomy 21
3 copies
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X-inactivation

• One X in females in transcriptionally silenced
• Xist RNA made that coats silenced chromosome
• Heterochromatin
• Why?
• Maternal or paternal X is randomly chosen in
  humans
• Not all genes on the X chromosome are silenced
• Calico cats
• Gene controlling hair color on the X-chromosome
• At early blastocyst stage

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XYY

• Usually non-disjunction of Y chromosome during
  sperm formation
• Estimated that 1 in 1000 males are XYY males
• Side effects increased height, acne, learning
  disabilities,
• Controversial link to increased violent behavior

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Fragile X

• Names for fragilesite on X-chromosome
• Long faces, big ears, autism, speech defects,
  sterile
• Usually affects males
• Why?
• FMR1 gene adjacent to the fragile site
• Shuttle protein for mRNA transport
• Important for brain development
• Promotor of FMR1 has a CGG repeat
• Gets methylated and blocks expression
• Expansion of CGG repeats determines severity

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Cancer

• Uncontrolled growth
• Invasion of adjacent tissues
• Metastasis
• Spread to other locations
• The cell cycle is HIGHLY regulated event
• When this event becomes unregulated? cancer

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Major signaling pathways relevant to cancer
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(No Transcript)
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Retinoblastoma

• RB1 is tumor suppressor
• Controls cell cycle
• Cells arrest at G1/S
• Need 2 non-functional copies to get cancer
• Familial RB1 individuals have an increased change
  of getting cancer
• Inherit one non-functional copy
• Easier to mutate 2nd copy to get cancer
• Uncontrolled replication
• cancer

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Pathway to retinoblastoma
mutation
mutation
Pair of chromosomes RB1 in red
Cancer
Familial RB1 mutation
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CML

• Uncontrolled replication of myeloid cells
• Chromosomal translocation between 9 and 22
• C-abl kinase under control of overactive promotor
• Drives cell division
• CANCER
• Not inherited
• Why?