Ch 6b

Question 1

Define polymorphism

Answer 1

Risk of toxic effects or cancer for an individual depends on exposure to a high enough level of a toxin & the individuals genetic predisposition

Question 2

what is Genetic predisposition reflected by

Answer 2

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

Question 3

give some examples of polymorphism in the human genome

Answer 3

• 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

Question 4

Define Dominant allele

Answer 4

the form of a gene in a diploid organism that is expressed

Question 5

Define ecogenetics

Answer 5

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

Question 6

pharmacogenetics

Answer 6

the study of differences in response of individuals to pharmaceuticals based on genetic variability
- over 120 known disorders

Question 7

Monogenetic trait

Answer 7

a characteristic that is encoded by a single gene

ex - phenylketonuria

Question 8

Polygenetic trait

Answer 8

one determined by many genes

ex - blood pressure, obesity, asthma

Question 9

Modelling polymorphism in a population

Answer 9

the presence of two or more subgroups in a population represents polymorphism

Question 10

what can determine if there is polymorphism

Answer 10

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

Question 11

What is one example of human polymorphism in environmentally relevant susceptibility genes

Answer 11

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)

Question 12

What is an example of human polymorphism in environmentally relevant susceptibility genes

Answer 12

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)

Question 13

Give an example of human polymorphism in regards to biological warfare purposes

Answer 13

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

Question 14

Give 4 reasons why there is speculation that PON1 polymorphism may be related to Gulf Ward syndrome

Answer 14

1. lines found in some but not all soldiers in a given unit
2. illness severity with a given unit were equally exposed
3. assumption: all members of a given unit were equally exposed
4. individuals with low/low phenotype for PON1 appear to have been more protected against neurological symptom complexes in Gulf War Veterans