1 - Fundamental Molecular Biology Flashcards
What is a mutation and net mutation?
A change in the genetic material of a cell/virus - not all heritable, can be due to radiation.
Net mutation = DNA damage minus repair.
What is the rate and basis of spontaneous mutations?
- Occur at very low rate
- Required by natural selection to generate genetic differences
- Arise from replication/repair errors, by-product of metabolism, mutagens and ionising radiation.
What do random mutations effect?
Mainly unimportant regions (silent) like between genes and exons.
This means they do not affect phenotype, but can affect key functional residues and regulatory regions.
What are the types of point and frameshift mutations?
Point - none, missense (aa), nonsense (stop).
Frameshift - INDELs (insertion or deletion).
What does most mutations being recessive mean?
They can only affect homozygous genotypes as recessive mutations require inbreeding - two carriers breeding is only way. It is also more common for loss of function (damage) than and advantageous change.
What is albinism?
The failure to convert tyrosine into melanin, phenotype is caused by lowered production of product.
> Mutation in OCA1
What is cretinism?
Lowered production of product.
What is PKU?
Treated via low phenylalanine diet - gene encodes phenylalanine hydroxylase and phenotype is caused by build-up/excess of substrate.
What is alkaptonuria?
Dark urine - build-up/excess of substrate.
What is the level of enzyme activity in recessive mutations?
Less or no activity.
How are mutations passed on and what does this mean?
Passed on via germline cells - these differentiate into somatic cells, which are genetic dead ends and disposable to natural selection - hence the rate of mutation is higher in soma.
How do dominant mutations arise (3)?
- Increase in enzyme activity
- Higher protein production
- New enzyme function
What is achondroplasia?
- Dwarfism, autosomal dominant
- Non-conservative missense mutation
- Slows limb growth
- FGF more active
What is Huntington’s Disease?
- Autosomal dominant
- Longer CAG repeat causes toxic protein
- Number of repeats can increase over time so is a progressive disease
What are de novo mutations?
They are new and not from parents germline.
What are orthologs?
- By common descent
- Probably have same role/function
- Infers interchangeable sequences
What are paralogs?
- By duplication
- Differ in roles/functions
- Model organisms
What is homology?
Biological features including genes and their products that are descended from a feature present in a common ancestor.
- Can explain genomic evolution.
What are INDELS?
Insertion or deletion mutations which are common and small. Affect protein product if they occur in exons, but not gene function as they occur outside genes, introns etc.
What are VNTRs?
- Variable number of tandem repeats aka micro/mini-satellites.
- Stable (passed down)
- Micro seen in Huntington’s
What are CNVs?
Copy number variants which are common in chromosome segments.
What is the difference between a variant and a polymorphism?
Mutant allele has frequency of….
Variant - <1%
Polymorphism - >1%
What is the molecular definition of evolution?
A change in the allele frequency over time in a gene pool.
What are SNPs?
Single nucleotide polymorphisms - affect protein product if inside reading frame, do not cause phenotype as they occur outside genes, introns etc.
What is the Hardy-Weinberg equilibrium?
If allele frequency is at equilibrium, then the observed genotype ratios will equal the predicted values of the H-W equation.
By using a pair of allele frequencies, we can predict the diploid genotype frequencies that keep allele frequency constant from one generation to the next - no evolution will occur.
P = A
q = a
2pq = Aa
When will allele frequencies be at equilibrium?
If they do not change with time, then the genotype frequencies will also stay at constant predicted values = equilibrium.
What does H-W assume (for no evolution to be occurring)?
- Alleles are stable
- From large homogenous populations
- Random mating
- All genotypes equally fit
