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
Germline Mutation
Mutation that occurs in every cell in an individual (inherited)
Somatic Mutation
Mutation occurring only in a subset of somatic cells
Phenotype will depend on what tissues are affected, and to what extent
Hemophilia A
Mutation to Factor 8
Allelic Heterogeneity
Occurrence of more than one disease causing allele at a locus
Mitochondrial Depletion Syndrome
Charcot-Marie-Tooth Disease
Locus Heterogeneity
Association of more than one locus with a specific clinical phenotype
Example: Two deaf people having normal offspring
Clinical Heterogeneity
Variability in relation to presentation or treatment of a disease.
Can be affected by lifestyle and environment
Example: Cystic Fibrosis traits,
Modifier Genes
Genes that affect the occurrence or severity of a phenotype associated with mutations in a non-allelic gene.
What type of heterogeneity does CMT display?
Locus and Clinical Heterogeneity
Epigenetics
Factors that can affect gene function without changes in DNA sequence
Examples: Prader-Willi, Angelman
Epiallele
Alleles of genes containing epigenetic marks
Histone modification, DNA methylation
Gene Silencing
Inactivation of a gene
Imprinting
Sub-type of gene silencing; normal function of cells.
If non-silenced gene is absent or mutated, can result is disease
(PW, AM)
Angelman Syndrome
Paternal Imprinted
Maternal Deletion
Prader Willi Syndrome
Maternal Imprinted
Paternal Deletion
