Genetic Variation Flashcards
What are Mutations?
hereditable change in the base sequence of genes
What are Genetic Variations?
Arise from Mutations that are positively selected described as DNA polymorphism
What is DNA polymorphism?
Any difference in Nucleotide sequence
What are the 5 reasons Mutations can arise?
- Strand breakage - lose nucleotides
- Base loss - broken glycosidic bond
- Base change - guanine is oxidised
- DNA crosslinking - UV light
- DNA replication error - errors not corrected
What happens when DNA repair mechanisms fail?
Leads to genetic damage
What are the health consequences for DNA not being repaired?
- Cancer susceptibility
- Progeria
- Neurological defects
- Immunodeficiency
Why do changes in DNA most commonly arise from?
Errors in DNA replication
What is the Mutation Rate?
If it is too low organisms cant adapt, if it is too high information cant be retained
What has the highest mutation rate?
Mitochondrial Genome
How does Genetic Variation arise?
As a consequence of mutation - Recombination (crossover events in meiosis)
What are the 3 Types of Mutations?
- Point Mutations
- Insertions/Deletions
- Chromosomal Mutations
What is a Point mutation?
- Changes to a single nucleotide (substitutions)
- Missense and nonsense mutations
What is a Chromosomal mutation?
- Polyploidy - multiple sets of chr
- Aneuploidy- abnormal number, extra/missing chr
- Chromosome rearrangements - parts moved to other chr
What is a Missense mutation?
A change in nucleotide sequence that results in a change to AA sequence
What types of Missense mutations are they?
Point mutations
Frameshifts
Loss of function (PAH) Gain of function (Achondroplasia)
Could effect protein function
What is a Nonsense mutation?
A change in nucleotide sequence that results in premature stop codon caused by point mutations and frameshifts
What does Nonsense mutations result in?
Non-functional protein
PAH mutation in BMPR2 gene
Duchenne muscular dostrophy- dystrophin gene
What are Insertions/Deletions?
Remove 1 to millions of nucleotides 5-10% all mutants 50% DMD frame shift a-thalassemias associated with melenoma
What Instrument can you Identify Gene mutations on?
Electropherogram
What are the features of Pulmonary Arterial Hypertension?
Intimal fibrosis
Direction of blood flow
Media thickening
What are Expanding trinucleotide repeats?
Simple tandem repears, during replication increase in copy number
- 17 diseases include huntingtons diseas
What happens in Huntington Disease?
- CAG repeats encode a poly-glutamine region
- In IT15 gene encoding huntington protein consists of 6-35 repeats
- 36 or > causes neurodegenerative disease
- raises ethical issues during genetic screening
What are Transposons?
Sequence of DNA that can move around the genome act as recombination hotspots
What are the 3 Types of Transposons?
Retrotransposonss - ‘copy and paste’
DNA transposons - ‘cut and paste’
Alu Repeats- most abundant, in LDL receptor for pathogenic deletions, also removes bad cholesterol eg FH
