What is polymorphism?
An allele is the form of a gene that you have – there are many different forms of most genes that still result in “normal” functioning.
How does polymorphism occur?
Can be a result of single base pair changes, insertions, deletions, etc.
Risk of toxic effects or cancer for an individual depend exposure to a high enough level of the toxin and _____
The individual’s genetic predisposition
What is genetic predisposition
Genetic predisposition is reflected by what alleles you have inherited from your parents
Is there a lot or a little polymorphism in the human genome?
There is a considerable amount
In a clinical trial do all people react the same to the drug?
- no some people will be severely affected and others will be unaffected due to polymorphism
Do all diseases have an environmental component that can interact with the genetic predisposition of the individual involved
this is likely
Define dominant allel
The form of a gene in a diploid organism that is expressed
Define Ecogenetics
Study of variability in genes in response to any environmental agent
What is the range of variability in genes?
10 to 40 fold
In ecogenetic studies do they just focus on genes expressed in the liver and hepatic portal area
no
Define Pharmacogenetics
The study of differences in response of individuals to pharmaceuticals based on genetic variability
What is the distribution of disorders caused by different responses to pharmaceuticals based on genetic variability
- 1/3 metabolic defects
- 1/3 receptors/transporters or channel defects
- 1/3 unclassified disorders
Define Monogenetic trait
a characteristic that is encoded by a single gene
What is an example of a monogenetic trait
phenylketonuria
- Cant convert phe to tyr
- can lead to impaired neural development if not detected and treated with low phe, high tyr diet
- now known to be effected by modified genes
Define polygenetic trait
one determined by many genes (i.e. blood pressure, obesity, asthma, ect)
what does the number of possible genotypes and phenotypes depend on
how many genes are involved
How many genes contribute to a risk of coronary heart disease
100
What is the frequency needed for the most common allele in a population for it to be considered polymorphism for modeling
no greater then 0.99 (minor allele frequency must be at least 0.10)
-rare alleles have a frequency of 0.01
Explain G6PD as an example of human polymorphism in environmentally relevent susceptibility genes
- Glucose-6-phosphate dehydrogenase is an enzyme thats activity is essential for generating NADPH and the re-oxidation of reduced glutathione
- The antimalaria drug primaquine causes acute hemolytic anemia in some individuals deficient in G6PD
Why do we care about NADPH
(electron carrier for biosynthetic processes
Why do we care about glutathione
(Helps the cell keep SH groups on proteins and Fe2+ in a reduced state)
