Genetics: Test 2

  1. ATP is produced in the respiratory chain by
    oxidative phosphorylation
  2. Mitochondrial defects may cause decreased _____.
    Result =
    • energy production
    • Result= "any sign in any tissue or organ at any age"
  3. Mitochondrion contains its own genome.
    DNA self-replicates within mitochondria.
    Each mitochondria has several copies of mtDNA (5-10)
    Each cell has many mitochondria
  4. Mitochondria are abundant in oocyte.
    How many mitochondria are found in sperm?
    4, located at the neck, typically do not enter the ovum
  5. mtDNA codes for __ genes
    Oxphos polypeptides?
    • mtDNA = 37 genes
    • 2 rRNAs
    • 22 tRNAs
    • 13 Oxphos polypeptides
  6. What has a higher mutation rate, mtDNA or nuclear DNA?
    mtDNA has a mutation rate that is 10x higher than nuclear DNA
  7. Mitochondrial mutations accumulate as we age; therefore, mtDNA mutations are found even in healthy individuals
  8. A cell may have a mixture of normal and mutant mitochondria.  This is referred to as?
    Heteroplasmy and is due to replicative segregation of mitocondria during mitosis.
  9. Which organs or tissue are the most vulnerable to mitochondrial disorders?
    Tissues that have high energy requirements.
  10. Defective OxPhos causes an increase in _______ in mitochondria and the cytoplasm.
    reducing equivalents
  11. Elevated NADH/NAD ratio leads to elevation of ?
    Leads to impaired function of?
    • elevation of Plasma lactate
    • impaired function of TCA
  12. Provocative tests for mitochondrial disorder
    • Glucose tolerance test
    • Measure CSF lactate, pyruvate if plasma values are normal
    • Plasma lactate and pyruvate after exercise
  13. Progressive adult muscle weakness.
    Fatal infantile myopathy
  14. How to diagnose a mitochondrial myopathy diagnosis
    • Muscle biopsy
    • Light microscopy
    • Electron microscopy
  15. MERRF
    • Myocloniec Epilepsy
    • Ragged Red Fibers
    • Generalized muscle weakness
  16. 80% of MERRF mutation people have a mtDNA mutation in what gene?
  17. MELAS
    • Mitochondrial Encephalomyopathy
    • Lactic Acidosis
    • Stroke-Like episodes, recurrent
  18. MERRF have mutation in
    MELAS have mutation in
    • MERFF= tRNA-lysine gene
    • MELAS= tRNA-leucine gene
  19. Kearns-Sayre Syndrome's symptoms are referred to as
    • "Opthalmoplegia Plus"
    • Ptosis, strabismus, pigmentary retinopathy, hearing deficit, ragged red fiber
  20. 8993T>G in the ATP6 gene most common mutation for mitochondria encephalomyopathy _____
  21. Diabetes mellitus shows some evidence of follwing a maternal inheritance pattern.  Mutation is in?
    3243 [tRNA9leu0]
  22. Subacute necorizing encepalomyopathy:
    Lactic acidosis
    Bilateral symmetrical focal regions of necrosis in the thalamus, pons, inferior olives (brain) and spinal cord

    Most cases are due to mutations in nuclear genes for ____
    Leigh disease

    Mutations in genes for OxPhos (Complex I, II, IV)
  23. •Skewed X chromosome inactivation can result
    in females manifesting signs of X-linked recessive disorders that are typically seen in affected malesExample:girls with Duchenne
    muscular dystrophy or with hemophilia A

    •Females with Turner syndrome and a 45,X
    chromosome constitution also manifest the clinical signs of an X-linked recessive disorder if their single X chromosome carries a mutant allele.

    •Females with an X-autosome
    translocation have preferential inactivation of their normal X chromosome (to
    maintain activity in the autosomal fragment), sometimes resulting in
    manifestations of an X-linked recessive disorder.

    •The union between an affected father and a
    carrier mother can produce a daughter affected with an X-linked disorder;
    always consider possible consanguinity/incest.
    Atypical X-Linked Effects
  24. EEC Syndrome (AD Inheritance)
    • Ectrodactyly
    • Ectodermal dysplasia
    • Clefting
  25. Isolated defects are the presentation of
    Multifactorial Inheritance
  26. Familial clustering of a trait with no distinctive Mendelian inheritance pattern.
    Recurrence risks are _____, not Mendelian
    • Multifactorial Inheritance
    • Empiric
  27. Multifactorial inheritance has much higher risk for ____
    Recurrence risks increase with the severity of the disorder
    • first-degree relatives
    • Ex. cleft-lip and palate
  28. Malformation Sequence
    Defect in neural groove closure prior to __ days
    • Neural tube defects (developmental pathogenesis)
    • Defect in neural groove closure prior to 28 days
  29. Neural Tube:  Anterior closure defect
  30. Neural Tube Defects:  Cervical and upper thoracic defect
  31. Neural Tube Defects:  Mid-to-caudal neural groove defect
  32. Myotonic Dystrophy is a repeat expansion mutation of
    • CTG (5-35 repeats)
    • Muscle weakness and wasting, facial wekaness, voluntary and percussion myotonia
Card Set
Genetics: Test 2
Mitochondrial Disorders