|
If humans were computers, then our DNA would be our "operating
system". However, just as loading incompatible software onto a computer,
or introducing a computer virus, can cause the operating system to crash,
so our actions and the substances we ingest can cause our DNA to stop
functioning properly and may even end up killing us.
Most of us have heard of, or
have known someone who suffers
from, a rare disease such as muscular
dystrophy (a severe, usually
lethal progressive muscle-wasting
disorder) or haemophilia (a bleeding disorder where
blood does not clot when one gets cut or bruised).
These are both conditions that result from faulty,
malfunctioning genes.
While these unavoidable conditions are very
sad for those affected by them, it is more frightening
to consider that even if we are born with
healthy, fully functional genes, this can change
during our lifetime, depending on the kind of
lifestyle we lead.
Cancer, heart disease, lung disease and diabetes
are the four most common types of diseases that
result from lifestyle-related (or non-communicable)
risk factors. In other words, these are the most
common conditions that we suffer from due to
living unhealthily. Basically, this means that by
living unhealthy lifestyles, we can actually damage
our healthy genes and have them turn against us!
You may be thinking that lifestyle-related diseases
are not likely to affect you at your age, and you are
hopefully right. But, that doesn’t mean that your
lifestyle while you are young isn’t going to affect
your health when you get older. Consider skin cancer.
When we are young, having a golden tan often
falls high on our priority list, while worrying about
the damage we could be doing to our skin does
not feature. The problem is that we only have one
skin that has to last our lifetime. Each time we
get burned, our skin suffers irreversible, long-term
damage that could eventually damage the DNA in
our skin cells and result in skin cancer.
The same applies to eating habits, exercise
habits, smoking and drinking habits, and while
no one will stop you from partying with reckless
abandon now, the one thing that you can be
sure of is that you are going to pay for it later.
For example, the World Health Organisation
(WHO) has predicted that if the growth in tobacco
use (smoking) goes unchecked, the numbers
of deaths related to its use will nearly triple,
from four million each year to 10 million each
year, in 30 years' time!
The good news is that the above lifestyle-related
diseases can almost always be avoided by simply
eating healthily, getting regular exercise, not
smoking and drinking in moderation. Well ...
most of the time anyway; our health can also be
damaged by living in unhealthy or polluted
environments. A recent study published online
by the Proceedings of the National Academy of
Sciences reported that mice subjected to the air in
close proximity to a steel mill had twice as many
genetic mutations as mice living in rural areas.
This is one of the first demonstrations of how
ambient air pollution exposure can result in gene
mutation.
In South Africa, we are particularly vulnerable to
environmental and pollution-related diseases such
as malaria, tuberculosis and cholera. Malaria alone
infects between 300 and 500 million people a year
and kills between one million and 2,7 million people,
mostly children.
As a result, scientists have made it a priority to
make the "mozzie" genome and the parasite that
it carries, the Plasmodium falciparum, some of the
first genomes, other than the human genome, to
be mapped. It is hoped that this is the first step in
finding out things like:
- why the mosquito prefers people to animals; and
- whether it will be possible to develop a vaccine
in future.
Scientists are also looking into genetically
engineering mozzies that don’t bite people or that
don’t carry the parasite, in the hope that this new
species will wipe out and replace the wild ones.
Without sounding like a prophet of doom, there is
yet another area where our genes can be negatively
affected by both our lifestyle and environment.
Allergies are reactions that some people experience
due to having "weak genes" that leave their immune
systems ill-equipped to break down some of the
proteins found in everyday foods. Among the most
allergenic foods are: peanuts, soybeans (found in
two-thirds of all manufactured foods!), wheat, tree
nuts, milk, eggs, shellfish and fish.
However, instead of trying to find ways to fix the
defective gene in the affected humans, scientists
are looking at ways of ridding the food of the proteins
that are causing the trouble in the first place.
Although research is far from complete and
no decisions have been made as to whether it will
be commercially viable, researchers like Anthony
Kinney at the DuPont Experimental Station in
Wilmington, Delaware in the US are experimenting
with a technique called RNA interference (RNAi)
with soybeans. This technique basically works to
silence the genes that code for protein 34,
the protein responsible for 65% of all soybean
allergies. RNAi serves to confuse a cell into
thinking that the RNA that carries the code for
protein 34 from the nucleus into the cytoplasm,
is a foreign agent. The cell consequently destroys
the RNA and effectively “turns off” this gene in
the cell.
Gene tests involve the examination of the DNA molecule. DNA
samples can be obtained from any tissue, including blood. In most
cases, a gene test involves scanning a patient’s DNA for mutated
sequences.
In some cases researchers use short pieces of DNA called probes,
whose sequences are the same as the mutated sequences for which
they are searching. The probes look for their twin among the three
billion base pairs of an individual’s genome. If the mutated sequence
is present in the patient’s DNA, the probe will stick to it, thereby making
it possible for the researchers to confirm that the mutation exists.
Another type of DNA testing involves comparing the sequence of
DNA bases in a patient’s gene, to a normal, or functional, version of
the gene in order to diagnose the presence or absence of a disease.
Unfortunately, DNA testing is usually very expensive depending
on the size of the mutated sequence that is being tested. The cost of
a DNA test can range from hundreds to tens of thousands of rands.
Genetic tests are used for several reasons, including:
- Carrier screening – which tests unaffected individuals who carry
one copy of a gene for a disease that needs two copies for the disease
to become active. In other words, if two parents carry the diseased
gene, then their children will inherit the disease.
- Prenatal diagnostic testing – which tests the amniotic fluid from the
uterus of an expectant mother, to see if the child has got a disease.
This procedure is known as an amniocentesis and is usually carried
out in pregnant women over the age of 35.
- Newborn screening – see “How will the HGP contribute towards the
prevention of disease?” on page 17
- Presymptomatic testing for predicting adult-onset disorders such as
Huntington’s disease. Huntington’s disease is a single gene disorder
of the central nervous system which usually develops in adult men
and women. It is caused by a faulty gene in chromosome four.
Unfortunately, it is not yet fully understood how the faulty gene
damages the nerve cells in areas of the brain, leading to gradual
physical, mental and emotional deterioration. Many people choose
not to be tested as there is, as yet, no cure for the disease.
- Presymptomatic testing for estimating the risk of developing
adult-onset cancers and Alzheimer’s disease.
- Tests to confirm a disease in someone who is already showing
symptoms of that disease.
- Forensic or identity testing – if a man wants proof that a child is
(or isn’t) his offspring, he can ask for DNA identity testing to be
done. DNA identity testing is also done when someone has died and
their remains make it impossible to identify them. These identity
tests can also be used to tie a criminal to a crime scene if no other
evidence is available.
Slight variations occur in less than 1% of our DNA sequence and produce different variants of a particular gene that is called alleles. These alleles determine how we look, among many other things, but is dependent on which genes are dominant or recessive.
As you already know, a person gets half his DNA from his
father and the other half from his mother. This means that he
ends up with two sets of genes, one set from his mother and
one set from his father.
Almost all our genes code for a particular protein, which may be:
- a structural constituent of a given tissue;
- an enzyme which initiates a chemical reaction; or
- a hormone.
Single gene disorders
In some cases a child may inherit an abnormal gene from his
mother or father, or from both parents. This abnormal gene may
or may not result in a single gene disorder, depending on whether
the abnormal gene is dominant or recessive.
For instance, if the father’s gene is defective and the
mother’s gene is normal, but there are no signs of the
defective gene causing a problem, then the father’s abnormal
gene is assumed to be recessive and the person is diagnosed
as having a recessive disease.
However, if the father’s defective gene does produce disease,
then the gene is said to be dominant and the condition is called
a dominant hereditary disorder. In some cases a couple that happens
to have the same recessive disease may only realise that they carry
the disease when their child is born and is discovered to suffer
from the disease. In many of these cases, there is a history of the
disease in both families and couples such as these should first
consider "carrier screening" before having a child.
The incidence of serious single gene disorders is estimated to
be about one in 200 births.
Other types of DNA-related disorders
But, single gene disorders are not the only types of diseases
that result from malfunctioning DNA. There are also:
- chromosomal disorders, such as Downs Syndrome, where
individuals have an extra copy of chromosome 21 (ie, they have
47 chromosomes instead of 46). This unbalanced set of genes
results in mild to moderate mental retardation and numerous
physical changes.
- multifactorial disorders: some of the most common diseases
such as coronary heart disease and cancer are the result of
the malfunctioning of numerous genes in our DNA.
- mitochondrial DNA-linked disorders: there are about 20 disorders
that have been found to stem from the malfunctioning of DNA in
the mitochondria of our cells (mitochondria has its own set of
DNA). Due to the fact that mitochondria come only from the egg,
these disorders are inherited exclusively from the mother.
A recent study done at the Massachusetts General Hospital
by Gary Ruvkin and Kaveh Ashrafi, is believed to have narrowed
down the pool of genes that may regulate fat storage in humans.
Based on the knowledge that there is more to staying thin
than just eating "lots of fruit and vegetables", these scientists
are looking to uncover the secret of why some people stay
effortlessly thin while eating whatever they want.
What makes the study so unique is that the findings are
based on the study of the genome of a microscopic worm called
Caenorhabditis elegans. The worm was used because about half
of the C. elegans fat genes have human counterparts.
However, this is just the beginning of the process and the
researchers now have to start testing the complementary genes in
humans to see if they are "wriggling" in the right direction.
Sickle cell anaemia is caused by a defective gene which codes
for haemoglobin - the part of the red blood cells that carry
oxygen around the body. As a result, the red blood cells are
deformed and are sickle-shaped instead of round. The blood is
sticky and doesn’t pass easily through the veins, preventing
oxygen from being delivered around the body. This causes
severe pain, anaemia, damage to the organs and can be fatal.
Sickle cell is caused by a genetic mutation that first occurred
during an epidemic of a deadly form
of malaria. It was found
that in areas where
malaria was a problem, children with one sickle cell gene
survived malaria, while those without the gene, died. This
shows that while this genetic mutation does cause sickness,
it also acts as a form of protection against malaria, thereby
showing that it has multiple functions. Sickle cell anaemia is,
as yet, incurable and studies are under way to use stem cell
transplants in children where the bone marrow (which produces
the blood cells) in the patient is destroyed using drugs and
replaced with healthy bone marrow from a relative, with normal
blood. The disease is most common in people of African and
Asian origin (20-30% of West Africans have the disease).
Why do some people last into their hundreds while others
check-out in their early sixties? While it’s well-documented that
lifestyle plays a major role in our length of life, there are still
those who eat, drink and smoke their way into their eighties. As
a result, researchers have concluded that our genes must also
play a part in deciding whether we are going to die young or just
keep clocking on the years.
Some research suggests that length of life is directly
proportional to fertility. In other words, the fewer children you
have, the longer you live and vice versa. Many parents would, no
doubt, agree with this theory!
Other research carried out on centenarians (people who live for
100 years or more), has discovered that these people tend to have higher
levels of an enzyme called polymerase 1, which reacts swiftly to repair
DNA damage when stress is applied.
However, it is hoped that the mapping of the human genome will finally
provide us with the recipe to living a long(er) life. But it is important
to remember that while our genes may endow us with a high
level of protection against the damaging factors that daily life
can bring, our lifestyle is always going to play a role in
determining how long we will last.
|
