Mutation + Single Gene Defects Flashcards
What is a mutation?
Heritable alteration or change in genetic material
What is a polymorphism?
Non-pathogenic alteration in DNA which may alter protein function but not usually deleterious
How do mutations occur
Errors in DNA replication/repair
Exposure to exogenous mutagens (smoke, radiation, chemicals)
What is a point mutation? Distinguish transitions vs transversions
Substitution of one base for another
Transition = purine to purine (A to G), pyrimidine to pyrimidine (T to C)
Transversion = purine to pyrimidine (A to C/T)
What is a synonymous vs non-synonymous point mutation? What are the two types of non-synonymous point mutation?
Synonymous = amino acid sequence unchanged due to redundancy of genetic code
Non-synonymous = does change aa sequence
— missense = replacement of one aa for another
— nonsense = replacement of one aa for stop codon
What does R117H or Arg117His mean?
Arginine residue 117 replaced by histamine
What does G542X or Gly542Stop mean?
Glycine residue 542 replaced by stop codon
What is a frameshift deletion/insertion?
Where number of nucleotides removed/added is not a multiple of 3, causing a shift in reading frame
What do frameshifts often cause?
Premature termination
Duchenne Muscular Dystrophy caused by? Therefore inheritance is…?
Exon deletions in X chromosome
X-linked recessive
What is anticipation, and what causes it?
More early onset of disease as you go down generations
Due to expansion of trinucleotide repeat sequences - become unstable during replication causing the replication of more repeats
The more repeats, the more protein function is affected
Why are triplet repeats more likely to expand?
Slippage during transcription, where repeats slip out of position and more triplets are transcribed than were there originally in the template
What triplet repeat causes Huntington’s disease?
Pathology and symptoms
> 35 repeats of CAG repeat in the huntingtin gene
Pathology = neuron degeneration in basal ganglia and cortical brain regions
Symptoms = unsteady gait and jerky movements, LATER they develop dementia
What triplet repeat causes myotonic dystrophy 1?
Symptoms?
CTG repeat in untranslated region of Dystrophia Myotonica Protein Kinase
Symptoms - muscle pain, myotonia (hyper excitability of muscle) , cardiac arrhythmias
Loss of function mutations tend to be dominant or recessive?
Recessive
What is haploinsufficiency?
When 50% of a functional gene is not sufficient for normal function
What is a dominant negative effect?
When a loss of function mutant protein is interfering with the function of the normal mutant
What is the cause of achondraplasia?
Mutation in fibroblast growth factor receptor 3, which normally inhibits enodochondral bone growth
Mutation will make the receptor function in absence of ligand - gain of function
Prader-Willi and Angelman syndromes are both examples of..?
Explain how each are caused
Imprinting diseases
Prader-willi when paternal (willys) SNRPN gene is abnormally methylated (switched off)
Angelman when maternal (angels) UBE3A gene is abnormally methylated (switched off)
