gene therapy Flashcards
Define genetic mutations
Changes in the nucleotide sequence of the DNA
Name 4 examples of spontaneous mutations
Replication error
Tautomerization
Deamination
Depurination
Name 6 examples of induced mutations
Intercalating agents Base analogues Deaminating agents Alkylating agents Oxidising agent Radiation
Replication errors
Some repetitive regions cause slippage and insertion of more repeats.
Can this be repaired?
NO
What is a replication error
Can it be repaired?
Normal replication introduces the wrong base once every 10^10 base pairs
Good chance it will get repaired
What is Tautomerization?
DNA bases can convert between forms altering the Hydrogen bonds
The tautomerization example of Amino to Imino is for what bases?
A or C
The tautomerization example of Keto to enol is for what bases?
G or T
What is deamination?
A bases looses an amino group
How many conversions of C to U happen per cell per day?
100
How many conversions of A to G happen per cell per day?
1
Which deamination can be repaired?
C A G can be repaired
T CANNOT BE REPAIRED
Define depurination
Cleavage of base-sugar bond on A or G is removed. So in replication the base pair is guessed
How many Purine glycosidic bonds are hydrolysed per cell per day
~10,000 purine glycosidic bonds
hydrolyse/cell/day
What are intercalating agents?
Insert themselves between bases
What is the results of base analogues?
Incorporated into DNA more prone t automeric shifts
What are alkylating agents?
Add alkyl groups to nucleobases
Name 2 examples of alkylating agents
Nitrosamines
Methyl Bromide
Can alkylation be repaired?
YES
What does Alkylation speed up?
Depurination
What are deaminating agents?
Remove amino groups far quicker than spontaneous deamination
Name 3 examples of deaminating agents
Nitrous acid
Nitrosamine
Nitrate
Nitrite
What mutagen causes the most mutations?
oxidising agents
Name an example of an oxidising agent
Superoxide ion O2-
hence H2o2
What are inborn errors of mutation?
A class of genetic disease involving altered metabolic function, eg mutation in a single gene encoding a metabolic enzyme
What are 3 types of metabolic disorders
Anabolic
catabolic
Storage
What type of metabolic disorder is Phenylketonuria?
Catabolic
Where is the gene mutation to cause Phenylketonuria?
Is it recessive or dominant?
Autosome 12
recessive
What enzyme is affected by a mutation in the Phenylketonuria?
Phenylalanine Hydroxylase
What does the phenylketonuria cause?
Inability to metabolise the essential amino acid Phenylalanine.
So excess phenyl-ketones in the urine and it builds up in the blood
mental retardation
organ damage
unusal posture
What percentages of the classic PKU point mutations are in ____ part of the PAH gene
intron/exon splice site
coding region
promotor
40% in intron/exon splice site 20% of mutations in coding region
40% in promoter
What is the normal result to increase Phe?
PAH enzyme converts Phe to Tyr
When does PKU mannifest?
What are the results for the sufferer?
Manifests after birth 1 in 20,000 newborns 5IQ lost /month Death by 20/30 years Must be put on low Phe diet
How many types of glycogen storage disease?
Is it dominant or recessive
14 different types
recessive
What is the problem caused by glycogen storage disease
Inability to convert glycogen to glucose
Enlarged liver
Hypoglycaemia
What are the 4 enzymes involved in glycogen breakdown
Glycogen phosphorylase
Glycogen debranching enzyme
Phosphoglucomutase
Glucose 6 Phosphatase
What causes Glycogen storage disease 1 - von Gierke disease
Phosphorylated glucose produced by glycogen breakdown is not readily transported out of cells
The liver contains glucose 6 phosphatase which cleaves glucose 6 phosphate into free glucose
Glucose 6 phosphatase is deficient in von Gierke disease
What causes Glycogen storage disease V - McArdle disease?
Which chromosome is this on?
The muscle glycogen phosphorylase is absent.
Myophosphorylase (PYGM) on chromosome 11.
How many different mutations in the gene
33 different mutations throughout the gene. 1 in 100,000 20/30 yrs old.
What are the results of McArdle diease?
Muscle weakness and cramps
Ability to perform strenuous exercise is limited
Shows that utilisation of muscle glycogen is not essential for life
Can Familial hyperchlestrolaemia be treated?
Only the heterozygous form
with statins
Decreased production of LDL cholesterol.
Produces more receptors.
