Biochem Exam 2

  1. Autosomal dominant disorders
    - Postaxial polydactyly

    - Marfan syndrome

    - Neurofibromatosis type 1

    - Retinoblastoma

    - Huntington disease
  2. Autosomal dominant characteristics
    - Vertical transmission

    - no skipped generations

    - equal proportion of genders

    - may show father to son transmission

    - 50% of offspring from affected individual will also be affected

    - unaffected individuals do NOT have affected offspring

    - Aa is less severe than AA

    - Spontaneous mutations are common

    - the trait frequently shows variation in expression

    - the basic defect tends to involve a structural protein

    - Sex-limited disorders DO exist

    - In determining risk, which parent is affected is inconsequential
  3. Autosomal recessive inheritance characteristics
    - Horizontal transmission

    - skipped generations

    - equal proportion of genders

    - may show father to son transmission

    - 25% of offspring from affected individual is also affected

    - a high prevalence of a rare autosomal recessive disease suggests consanguinity
  4. Autosomal recessive diseases
    - cystic fibrosis

    - sickle cell disease

    - Hurler syndrome (a lysosomal-storage disease)

    - tyrosinase-negative albinism

    - achondroplasia
  5. Penetrance
    The probability a mutant genotype will have any phenotypic expression at all. It is measured as the percentage of people with a mutant genotype that are actually affected.
  6. Factors that may complicate inheritance patterns
    - Reduced penetrance (<100% penetrance)

    - Delayed age onset

    - Variable expression

    - Pleiotropy and Heterogeneity

    - New mutation

    - Germline mosaicism

    - Genomic imprinting
  7. Factor V Leiden mutation
    (example of AA more severe than Aa)
    = Increased risk of thrombosis

    Heterozygotes (4-7% of general population)

    - 5-7 times greater risk for DVT

    Homozygotes (0.06-0.25% of general population (up to 10% in S. Sweden and Greece))

    - 80 times risk for DVT
  8. Expression
    The degree of severity of a given mutant phenotype or disease and can range from so mild that the affected person is unaware of it to an extremely severe disease state.

    Variable expression- refers to the extent of expression of the particular disease phenotype
  9. Anticipation
    where more recent generations display more severe forms of an inherited disease
  10. Fragile X Syndrome
    - an X-linked dominant condition

    • - CGG repeats in 5'-UTR of FMR1 gene
    • (6-50 copies = Normal, 50-230 copies = Normal transmitting males, 230-1000 copies = Fragile X Syndrome)

    - Exhibits anticipation

    - NTM cannot transmit the disease to their daughters, but expansion of copies is seen through the daughters, and is represented in their offspring

    - These expansions do NOT occur in male transmission

    - Most common inherited form of mental retardation in males

    - Penetrance = 80% for males, 30% for females

    - >230 copies of CGG repeat = methylation of FMR1 (stops expression of gene) = no FMRP product = Fragile X Syndrome
  11. Lyonization
    One X chromosome in every somatic cell at the 16-64 cell stage of X females is randomly and permanently inactivated in that cell and in all its clonal descendants
  12. Characteristics of X-linked dominant inheritance
    - twice as many affected females as males

    - NO father to son transmission

    - Vertical transmission with no skipped generations

    - occurrence/recurrence depends on the affected parent's gender
  13. X-linked dominant diseases
    - Fragile X Syndrome

    - Hypophosphatemic rickets

    - incontinentia pigmenti type 1
Card Set
Biochem Exam 2
Biochem Exam 2