MCB Block 4

  1. Alpha Thalassaemias
    • Deleted a-globin structural gene
    • a-thal->HbH->hydrops fetalis
  2. Beta-Thalassaemia
    • Skull shape changes due to bone marrow hypertrophy
    • Point mutation that change length of exon
    • Not missense mutations
    • Hb-Lepore=unequal crossing over and promoter issues
    • Persistance of Fetal Haemoglobin-deletion of promoter element
  3. Nail-Patella Syndrome
    • Nail and elbow dysplasia, hypoplastsic patella, iliac horns
    • LMX1B-/-, Dominant
    • Haploinsufficiency-LOF
    • All mutation in the same gene give the same phenotype
  4. Achondroplasia
    • Short Stature
    • FGFR, Dominant (sporadic)
    • Gain of Function-Up regulation, Novel function
    • Typically missense
    • See also Hypochondroplasia and Thanatophoric Dysplasia and Apert
    • Different mutations of the same gene can result in different phenotype
    • Similar mutation in similar genes can results in different phenotypes if the genes are expressed in different cell types or at different times in development
  5. Osteogenesis Imperfecta
    • Dominant-negative
    • Mutant protein interferes with normal
    • Typical among structural proteins
    • Severe-mutant protein made
    • Mild-half of normal protein made (null)
    • Premature termination codons do not cause truncated proteins
  6. Polydactyly, Campomelic dysplasia, Lactose tolerance
    • Common birth defect
    • Distal element and enhancer mutation near SHH
    • Different enhancers can direct expression of SAME gene in DIFFERENT tissues
  7. Williams Syndrome
    • Distinct Facial features, loquacious, mental retardation
    • 7q11.23 deletion
    • With every deletion there is a corresponding duplication correlating symptoms and also total opposite symptoms
  8. Myotonic Dystrophy
    • Genetic Anticipation
    • CTG repeat in UTR; AD
    • Altered RNA function, GOF
    • Forward slippage = deletion
    • Backward = insertion (okasakis)
  9. Friedreich Ataxia
    • Neurodegenerative
    • Intronic Triplet Expansion (GAA); AR
    • Frataxin defiency by mRNA synthesis
  10. Fragile X Syndrome
    • Mental Retardation, Distinct facial features
    • X-linked Dominant
    • Null mutation, no protein
    • Normal transmitting males (causes skipping)
Card Set
MCB Block 4