Week 11

Week 11

Muscle Diseases
1. Skeletal Diseases
  1. duchenne dystrophy
    1. sex linked
    2. mutations in the protein dystrophin
    3. dystrophin is found in costameres that link the z disc to the sarcolemma
    4. leads to cell damage so muscles don't work
  2. arthrogryposis
  3. congenital myopathies
    1. central core
    2. distal myopathy
    3. hyaline body myopathy
    4. inclusion body myopathy
    5. limb girdle dystrophy
    6. nemaline myopathy
      1. mutation in actin and nebulin
      2. autosomal dominant and recessive
      3. exercising slows NM and keeps muscle levels at the appropriate level
      4. affects the level of muscle fibres
      5. 3 main features
        rods in sarcoplasm - aggregation of actinin and actin
        nuclear rods - actin cycles in and out of the nucleus on exportin 6 mutations can cause this to stop
        actinopathy - amino acids are replaced with different amino acids causing sarcomere-free areas which contain aggregates of actin
      6. mutations in skeletal actin are found all the way through actin
      7. nebulin
        binds to up to 200 actin monomers and spans from z line to the end of the thin filament binding to tropomyosin and tropomodulin
        mutations mean it can't bind to proteins on actin
      8. tropomyosin and troponin are also affected with various consequences
      9. cofilin - severs actin filaments, homozygous mutation causing mild early onset
  4. dystrophy - degeneration over time
  5. myopathy - no degeneration over time
    1. mutations in myosin can cause myopathies
    2. cardiomyopathy
      1. hypertrophic - thicken heart walls causes less blood capacity and reduced access out of heart
        disease of muscle sarcomere, myosin cant bind to actin which makes to heart make more myofibrils
      2. dilated - thinned heart walls cause inability to pump blood aswell and low blood pressure
  6. beneficial mutation
    1. alpha-actinin-3
    2. alpha-actinin is in the z line and expressed in fast muscle fibres
    3. sprint and power athetes are likely to have alpha-actinin-3 and endurance athletes not
    4. found in fast muscles fibres
    5. loss of actinin changes fast muscles to slow
    6. muscle mass decreases
    7. contractile properties of muscles slows
    8. fatigue resistance increases
    9. oxidative enzyme activity increases
Genetics and Disease
1. Mendelian Inheritance
  1. 11,000 traits or disorders on humans show single gene unifactorial inheritance
    1. trait or disorder on autosomal gene - autosomal inheritance
      1. dominant and recessive
    2. trait or disorder on sex chromosomes - sex linked inheritance
      1. dominant and recessive
      2. recessive affect males only
      3. dominant affects females more
    3. affect males and females equally
  2. Genetic Inheritance
    1. DNA is the pattern for inheritance
    2. problems can arise and mutations occur
2. Mutations
  1. a heritable alteration or change in the genetic material
  2. can occur following exposure to mutagens but majority occur from errors in DNA replication and repair
  3. somatic - can not be transmitted to offspring
  4. gonadal - can be transmitted to offspring
  5. harmful alleles constitute the genetic load of the population
  6. types
    1. chromosomal changes
    2. submicroscopic changes in one or more nucleotides
    3. were thought to be fixed or stable but now believed to be dynamic or unstable which means they can undergo further alteration as they are transmitted
    4. fixed/stable point mutations
      1. single nucleotide polymorphisms - replacement of a single nucleotide
      2. transition - substitution like for like
      3. transversion - substitution of pyrimidine for a purine or vise versa
      4. deletions - loss of one or more nucleotide distrupting the reading frame
      5. insertions - addition of one or more nucleotide distrupting the reading frame
    5. dynamic/unstable mutations
      1. triplet base repeat sequences
      2. increase in triplet base repeat sequences is amplification which is the basis for single gene disorders like huntingtons
      3. mechanisms not clear but repeats below a certain number are consistantly transmitted during mitosis and meiosis however some aren't - unstable mutation
      4. Enter text here
Diabetes Insipidus
Arthritis

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