Define polymorphism
Risk of toxic effects or cancer for an individual depends on exposure to a high enough level of a toxin & the individuals genetic predisposition
what is Genetic predisposition reflected by
by what alleles you have inherited from your parents.
- there are many different forms of most genes that still result in normal function, this can be a result of single base pair changes, insertions, or deletions
give some examples of polymorphism in the human genome
- within families; some individuals are more severely affected than others for inherited disease or results of exposure
- some people in a given pharmaceutical trial or environmental exposure are unaffected or severely affected
- likely that all diseases have an environmental component that can interact with the genetic predisposition of the individuals involved
Define Dominant allele
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
- variation in response can range from 10 to 40 fold
- genes of interest in these studies are not just expressed in the liver and hepatic portal area
pharmacogenetics
the study of differences in response of individuals to pharmaceuticals based on genetic variability
- over 120 known disorders
Monogenetic trait
a characteristic that is encoded by a single gene
ex - phenylketonuria
Polygenetic trait
one determined by many genes
ex - blood pressure, obesity, asthma
Modelling polymorphism in a population
the presence of two or more subgroups in a population represents polymorphism
what can determine if there is polymorphism
if the most common allele in a population has a frequency no greater than 0.99 then there is a polymorphism
- Minor allele: frequency of at least 0.10
- Rare allele: frequency of less than 0.01
What is one example of human polymorphism in environmentally relevant susceptibility genes
Glucose-6-phosphate dehydrogenase (G6PD)
- activity of this enzyme is essential for generating NADPH and the re-oxidation of reduced glutathione (glutathione helps the cell keep SH groups on proteins and Fe2+ in a reduced state)
What is an example of human polymorphism in environmentally relevant susceptibility genes
paraoxonase (PON1)
- enzyme activity: known to be an apoJ high-density lipoprotein-associated enzyme important in cardiovascular homeostasis
- appears to function in breaking down oxidized lipids and cholesterol that can deposit on arterial walls & lead to coronary heart disease
- can hydrolyze many toxic organophosphates & paraoxon (nerve gas)
Give an example of human polymorphism in regards to biological warfare purposes
organophosphates used in the Gulf war.
- western forces used pyridostigmine (competitive inhibitor for nerve gas) as a prophylactic vs possible nerve gas attack - it was thought to protect acetylcholinesterase by binding reversibly to it.
- useful because it doesn’t usually cross the blood-brain barrier therefore mental capacity is not affected
Give 4 reasons why there is speculation that PON1 polymorphism may be related to Gulf Ward syndrome
- lines found in some but not all soldiers in a given unit
- illness severity with a given unit were equally exposed
- assumption: all members of a given unit were equally exposed
- individuals with low/low phenotype for PON1 appear to have been more protected against neurological symptom complexes in Gulf War Veterans
