Disease Resistance and Susceptibility Genes
o can confer an increase/decrease in susceptibility to a disease (they do not necessarily
cause the disease but they increase the chances of acquiring the disease).
o Or they influence the severity of the disease (do no cause the disease themselves).
Disease Restriction Genes:
Example Resistance to AIDS
Some people were at high risk of AIDS (i.e. prostitutes), but did not get infected - this did not
Discovered that those individuals were homozygous for CCR5 (chemokine receptor 5)
Chemokine receptor 5 (if they were homozygous for this– they seemed to remain unaffected).
Also found people who were positive for 10 years or more with no disease progression (had
minor symptoms but did develop bull-blown AIDS).
o Concluded that they were heterozygous for this mutation.
There are several alleles for this receptor (CCR5).
Receptor that allows AIDS into cell is CD4 receptor (receptor protein in T-cells).
o Receptor that seems to be responsible for transporting HIV into the cell.
CCR5 is co-receptor for CD4.
CCR5 also has to act for the CD4 receptor to work properly (they must work together).
T- cell will remain uninfected if the CCR5 receptor isn’t working.
If homozygous – prevents development of AIDS/ heterozygous – delays development of
For recessive traits, must be homozygous to have the disease
Example of Malaria Resistance
Sickle cell disease – if you’re homozygous, you have this disease. If heterozygous, you will
generally be healthy (although up to 40% of red bloods cell will be affected). Heterozygous
people will also be resistance to malaria.
Theory: infection reduces circulation of red blood cell, decreases oxygen partial pressure.
Sickling will then lead to destruction of infected red blood cells – reduces ability to carry oxygen
- cells die.
Beta subunit of hemoglobin is affected - reduces synthesis of hemoglobin - less ability to
More severe than sickle cell…severe/lethal if you’re homozygous for disease. Heterozygous seem to be resistant to malaria.
o Being heterozygous gives protection against GI tract infection.
o As a result, this confers protection against diphtheria, cholera.
o Seems to give protection against cancer.
HTZ seemed to have reduced risk of miscarriage
And spontaneous abortions due to fungal infections.
o Allele confers resistance against tuberculosis (with one copy of allele).
Combine Susceptibility Resistance Genes
These are genes that reduce susceptibly of some illnesses but help us resist other types of ilnesses
Know what genetic influence is.
But if enzyme changes in some way, affects can vary according to environmental factors.
Most alleles don’t have single affect.
True for all genes?
Ex. G6PD deficiency
o One is deficient in this enzyme.
o 400 different alleles for this gene.
o Enzyme involved in glucose metabolism (RBC).
o If deficient in enzyme – RBC will die – Hemolytic anemia will develop (disease in which
RBC are being destroyed ).
o RBC can only be destroyed under certain circumstances.
o This pathology in which it destroys RBC occurs only under oxidative stress.
o So if one has this allele and this deficiency, its affects will not be noticed until RBC are
under oxidative stress where oxygen needs to be metabolized quickly.
o GENERALLY, in order for this to occur, certain environmental factors must be
present that will increase oxidative stress (these are called pro – oxidants).
o Ex. of pro – oxidants includes fava beans, moth bolls, sulfa drugs, antimalarial drugs – all
these can lead to hemolytic crisis (if deficient in enzyme).
o Different from sickle cell/ thalassemia because it is x-linked – thus, found predominantly
o Males - all cells will have it/ Females – some cell will have it.
o Allele produces some resistance to malaria (deficiency can render the affects).
Deficiency affects internal environment of RB unfavorably.
Malaria – part of its life cycle, the merozoids live in RBC, divide, and repeat
process in other RBC.
Since RBC environment is not favorable, merozoids die.
They will eventually adapt to environment, but delay development of malaria (if
RBC is affected by deficiency).
Resistance is less in males but if heterozygous (i.e. females), they will have more
resistance to malaria.
o A debate exists as to whether or not males are resistant to malaria: It is thought that they only have temporary relief.
Hypothesis: For females, the merozoids adapt to one particular type of RBC
(specific type of oxygen environment in RBC). If they affect the other type, then
they cannot survive.
So after the merozoids reproduce and leave, suppose you have half of RBC that
have deficiency and the other half don’t, there is a 50/50 chance of going to a
RBC that they can survive in and so on. Keeps # of merozoids under control.
Mutations reside in germ cells given to offspring during conception.
Many mutations won’t have a great affect on person (i.e. cell mutated to release toxins will not
have huge affect – will only affect surrounding cells).
However, what if a mutation in a cell occurred to have the cells to keep on dividing (even when
body reaches a point where cell division should stop)?
o Cells become cancerous – only mutation that can affect health.
Innate Factors in the Human Body and Health – Cancer
Cancer can stem from changes that occur in innate factors in our bodies.
Other words for cancer: Neoplasia, malignancy.
Impact of Cancer
o Lifetime risk of cancer (incidence) : 40% women / 45% men.
o 25% of all deaths – Cancer – Canada.
o Incidence rates peak when one is in their 60’s.
o Mortality peaks in 70’s or 80’s.
o Second leading cause of death.
o Before 75 – is first cause of death.
Did we win war on cancer?
Problem is unique
Need to determine the size of the problem of cancer.
o If size of problem can be determined, we can find out whether we are winning or losing
war on cancer.
How to determine size of problem?
1. Determine incidence.
o Lung cancer is declining (decrease in smoking).
Effects of diagnosis? (Publicity campaigns encouraged people to get screened)
These publicity campaigns could be one reason rates in cancer increases – bc
more people went out and got screened.
2. Mortality rates: Use 5 – year survival rate, if you survive within those years, you’re considered
Rate has been increasing since 1970’s
o Due to early detection
o Increased screening since 70’s – people getting diagnosed earlier.
Potential biases o Screening bias (do people who volunteer to get screened more healthy or
interesting in their health?)