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Alpha Thalassaemias
- Deleted a-globin structural gene
- a-thal->HbH->hydrops fetalis
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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
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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
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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
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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
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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
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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
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Myotonic Dystrophy
- Genetic Anticipation
- CTG repeat in UTR; AD
- Altered RNA function, GOF
- Forward slippage = deletion
- Backward = insertion (okasakis)
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Friedreich Ataxia
- Neurodegenerative
- Intronic Triplet Expansion (GAA); AR
- Frataxin defiency by mRNA synthesis
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Fragile X Syndrome
- Mental Retardation, Distinct facial features
- X-linked Dominant
- Null mutation, no protein
- Normal transmitting males (causes skipping)
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