Sollars - Principles of Genetic Disease Flashcards
Frameshift Mutation
Insertion/Deletion of nucleotides in non-multiple of three; cause entire reading frame after mutation to be misread
Types of RNA Processing Mutations
Promoter Mutations
RNA Processing Mutations
Regulatory Protein Mutations
Transposon Insertion
Waardenburg Syndrome
Most common syndromal cause of deafness
Autosomal dominant
Pigment disturbance; wide nasal bridge
Loss of Function Mutation
Change in a gene negatively affecting amount of function of a gene product
What is sufficient for health for most inborn errors of metabolism?
One functional allele
Haploinsufficiency
50% not sufficient for normal function
Gain of Function Mutation
Change in a gene, resulting in a gene product that is usually biologically harmful
May result in a novel protein product, more commonly over-expression or inappropriate expression
Dominant Negative
When defective protein is not only nonfunctional, but inhibits function of normal counterpart
Example: Osteogenesis Imperfecta
Polymorphism
A mutation that is relatively abundant (>1%) in a population
ex: Rh+, Rh-
Many are silent mutations
Silent Mutation
Gene mutation that has no consequence at the phenotypic level
Dosage Sensitivity
The level of protein product produced by a gene can produce different phenotypes at various levels, rather than one absolute phenotype for present/not-present
Examples are CMT1, CMT2, and CMT3
Charcot-Marie-Tooth Disease
Displays locus heterogeneity
Most common inherited neuropathy
Demyelination, weakening of muscles, decrease in sensory functions
Charcot-Marie-Tooth Disease Type 1A
Duplications in PMP22 (Chromosome 17)
Autosomal Dominant
Hereditary Neuropathy w/Liability to Pressure Palsies (HNPP)
or
CMT 1B
Deletions in PMP22 (Chromosome 17)
Autosomal Dominant
Sausage shaped nerves (generally less severe)
Dejerine-Sottas Syndrome (DSS)
or CMT3
Point Mutations in PMP22 (Chromosome 17)
Autosomal Recessive
Like CMT; very severe; occurs in infancy
