|
Frequently Asked Questions
Q. Are all diseases caused by genes?
A. Some severe but relatively rare disorders are
"caused" by the expression of a different form
(allele) of a single gene. These are known as single gene
or monogenic disorders. These diseases include:
- Cystic fibrosis
- Huntington's disease
- Hemophilia
Many common diseases that affect many millions of people
worldwide arise through complex interactions between the
environment and a number of genes known as susceptibility
genes. Different forms or alleles of susceptibility genes
alter the risk of the disease developing or its severity.
These diseases include:
- Late onset Alzheimer's disease
- Adult onset diabetes
- Cardiovascular disease
- Asthma
- Parkinson's disease
- Migraine
- Schizophrenia
- Depression
- Chronic obstructive pulmonary disease
- Osteoarthritis
Other diseases are caused mostly by environmental factors,
with genes playing a minor role. Examples of these conditions
are infectious diseases that arise due to exposure to a
specific pathogen (such as a virus or bacteria) in the environment.
Q. How does my healthcare provider use genetics as part
of my care?
A. A patient's family history — which is really
a kind of genetic history — is an important aspect
of a physician's examination and can provide important clues
to the patient's condition. This is nothing new —
it has been common knowledge and standard practice for a
long time.
Although physicians have known that family history, or
genetic makeup, affects disease susceptibility, they have
not known what specific gene changes are responsible for
increasing the risk of disease. With a few exceptions, identifying
gene variations related to disease is difficult, and the
necessary techniques have become available only in recent
years. Even now, the number of diseases for which a "genetic
diagnosis" will assist in diagnosis and treatment is
limited.
The future may be different. It may be possible to use
genetic information to diagnose diseases more accurately
and to predict a patient's likely response to a particular
medicine or treatment.
Q. How do health care providers prescribe medicines today?
A. Today's practice of medicine is based on a sophisticated
understanding of human physiology, a wide array of sensitive
diagnostic tests and a variety of effective treatments.
However, many medicines are prescribed and then evaluated
in an individual patient to determine if the patient is
receiving the most suitable medicine at the correct dosage.
This "hit or miss, one-size fits all" approach
potentially exposes patients to serious side effects without
expected benefits and is inefficient both in terms of treating
the patient's condition and of physician and patient time
and cost.
Patients can experience serious complications as a result
of their medication. In the United States during 1994, an
estimated 3.6 million patients experienced an adverse drug
response while hospitalized and another 1.5 million were
hospitalized as a result of such a reaction. More than 2
million of these adverse events were considered serious.
The financial burden of inappropriate use of medicines for
individual patients also is considerable. The Pharmaceutical
Researchers and Manufacturers of America estimate that underdosing,
overdosing and missed doses cost the United States >
$100 billion a year in increased hospital admissions, lost
productivity and premature death.
Some serious side effects may be inevitable with some medications,
such as cancer drugs, and patients need to follow instructions
for taking medications as ordered. However, helping healthcare
providers to more accurately prescribe the right medicine
at the right dose for an individual could result in major
benefits to patients, health care providers, insurers and
society.
Q. What does "getting the right medicine to the right
patient" mean?
A. The majority of patients respond well to medicines,
while others don't respond as expected or have serious side
effects. For example, some people develop a rash when they
take penicillin. If a particular version of a gene (allele)
or combination of alleles predisposes some patients to this
reaction — and if physicians can identify patients
who have this gene variant before they prescribe the drug
— then the rash can be prevented by using another
antibiotic.
As a research-based pharmaceutical company, we at GlaxoSmithKline
believe we can use the results of genetic research to discover
why people respond differently to the same medicines. With
that knowledge, we can create new medicines and help physicians
choose the right medicine for the right patient.
Q. Have recent strides in genetic research influenced
the practice of medicine?
A. Not appreciably, but new findings will greatly
influence the future practice of medicine. In fact, genetics
may completely change the way diseases are defined. Whereas
we now identify and treat a disease as a set of observable
signs and symptoms (phenotype), we are learning that it
may be possible to identify and treat disease based on genetic
information (genotype) as well as phenotype. For example:
- Colon cancer was once thought to be
a single disease. However, the use of genetics has made
it possible to detect a difference between two types:
a single-gene disease with a very strong genetic component
and an occasionally occurring disease with a weak genetic
component, but a strong environmental influence (i.e.
diet). Knowing which type of the disease is present has
an important impact on its treatment and even prevention.
- Another company is marketing a gene
testing service to aid neurologists in diagnosing some
genetic forms of Alzheimer disease.
- A European company developed a gene-specific
test to enable physicians to identify patients likely
to show a positive response to treatment of high blood
pressure with a specific type of medicine (angiotensin
converting enzyme (ACE) inhibitors).
Q. What are "susceptibility genes"?
A. Susceptibility genes are variations in specific
genes that alter the risk of developing a disease. Many
common diseases arise through a complex interaction between
many susceptibility gene variants and the environment.
Q. What is involved in identifying genes that are associated
with disease, and why is it so time-consuming?
A. DNA is packaged into chromosomes inside our cells
(in the nucleus). Human DNA, which contains an estimated
30,000-40,000 genes, is made up of three billion pairs of
chemical bases. These bases are arranged like letters to
spell out words that instruct the cell to make particular
proteins. A change in just one of the three billion base
pairs can cause disease or increase the risk of disease.
In order to find the gene variations (alleles) that are
related to a disease, the location of the gene or genes
on the chromosomes need to be identified. One way of doing
this is by studying the disease in families affected by
it or in the general population to determine if one or more
particular markers (located on a specific part of the chromosome)
is inherited with the disease.
Markers, like highway signs, can point to particular places
where disease-related genes and alleles may be found. Once
a likely region of the chromosome has been identified, the
search for the disease gene can be focused on this region.
Researchers use a process called "DNA sequencing"
to identify the order of base pairs in the region and to
look for differences (e.g. a mutation) between the DNA of
those who have disease and those who do not have the disease.
Given the high number and extremely small size of genes
and base pairs, it is easy to understand the challenges
of sequencing DNA. It's made even harder because almost
all human DNA is the same. The individual differences we
see in people — their hair and eye color, height,
and other characteristics — are due to differences
in only 0.1% of their DNA; the remaining 99.9% is the same
in everyone. This is like reaching your hand in a jar of
1000 white marbles and trying to find the one with a tiny
yellow dot on it. So it is not an easy task for scientists
to find the genetic differences between people that play
a role in disease.
|
