1. bisphosphenol A
    "an estrogenic compound that appears to disrupt normal chromosome formation & recombination & segregation in fetal ovaries; leads to ""grandmother"" effect; interferes with estrogen receptor beta"
  2. aneuploidies that are compatible with life
    13; 18; 21
  3. egg vs. sperm lifespan
    egg = 10-50 years; sperm = about 50 days
  4. Favry disease
    an LSD; results in failure of many organs if untreated; symptoms = hypohidrosis & acroparesthesias & cornea verticillata & angiokeratomas & pain attacks; therapy = enzyme replacement therapy; X-linked but most females = symptomatic
  5. LSDs
    lysosomal storage diseases; describes a group of approximately 40 genetic disorders; caused by deficiency in one enzyme that results from an inborn error of metabolism; therapies include enzyme replacement therapy & stem cell transplant & substrate reduction & enzyme enhancement
  6. Gaucher disease
    most common LSD; glucocerebroside deficiency; causes engorged macrophages which lead to enlarged spleen and liver; some forms can be treated with enzyme replacement therapy
  7. Krabbe disease
    autosomal recessive disorder that results in degradation of the myelin sheath; results from mutations in the GALC gene that lead to deficiency of the enzyme galactocerebrosidase
  8. MPS
    an LSD; mucopolysaccharidosis; defects in enzymes responsible for the degradation of mucopolysaccharides lead to buildup of toxic metabolites; results in progressive physical deterioration and mental retardation
  9. targets for genetic disorder therapies
    whole-body; organ; cellular; protein; metabolite; chromosome; RNA; DNA
  10. chaperone therapy
    could supplement enzyme activity; advantages: are generally small & can be taken by mouth; disadvantages: will not work if no enzyme present & may chaperone similar proteins & may not work for all genotypes
  11. fragile X syndrome
    transmitted via sex-linked dominant loss-of-function mutation; trinucleotide repeats (>200) in 3' untranslated region results in absent FMR1 gene; lack of FMRP product leads to increased mRNA translation (possibly via mGlu5 receptors) and decreased synaptic plasticity; most common cause of mental retardation
  12. Friedreich's ataxia
    transmitted via autosomal recessive loss-of-function mutation; trinucleotide repeats (>200) in intron region; reduces levels of frataxin (protein localized to inner mitochondrial membrane that may play a role in reducing damage from free radicals); results in degeneration of spinal and peripheral nerves
  13. locations of dynamic mutations
    5' untranslated; intron; exon; 3' untranslated
  14. fragile X-associated tremor ataxia syndrome
    gain-of-function RNA-mediated disorder; may result from sequestering of RNA-binding protein on the CGG-repeat expansion (preventing other necessary functions); results from premutation repeats in the fragile X locus but is mechanistically unique from fragile X syndrome
  15. Sherman paradox
    refers to pattern of inheritance in fragile X syndrome; genetic anticipation
  16. myotonic dystrophy
    gain-of-function RNA-mediated disorder; autosomal dominant inheritance pattern; wide expressivity; results in mutation on 3' untranslated end of DNA; repeats sequester splicing factors and prevent them from splicing other genes
  17. Huntington disease
    gain-of-function protein-mediated disorder; autosomal dominant inheritance pattern; results in loss of medium spiny neurons and atrophy within caudate and putamen; results in production of many glutamines which alters function of Huntingtin protein
  18. Ataluren/PTC124
    drug that reads through nonsense mutations; can be taken by mouth; development still in progress
  19. cystic fibrosis
    caused by mutation in the CFTR gene (codes for chloride channel) - leads to abnormal ion transport and fluid imbalance; buildup of mucous causes blockage of breathing passages and lungs & pancreatic deficiencies
  20. mitochondrial diseases
    characterized by: maternal transmission; manifestation in tissues that require a lot of energy (many mitochondria); multi-organ manifestation; red ragged fibers (clumps of diseased mitochondria) in muscle; heteroplasmy (threshold effect) and mitotic segregation (random distribution of diseased vs. non-diseased); treatment = supportive & symptomatic
  21. locations of mutations leading to mitochondrial diseases
    can be in nDNA (majority) or mtDNA or communication in between; structural components of respiratory chain; ancillary proteins; inter-genomic signaling pathway; mitochondrial-protein-insert machinery
  22. characteristic lab findings for mitochondrial diseases
    ragged red fibers (muscle biopsy); sensorineural hearing loss; cardiac conduction defects; defective oxidative phosphorylation; myopathic potentials; basal ganglia calcification/MRI abnormalities
Card Set
Genetic disorders