Gene Cloning

Forensic and Medical Applications 421
find correlations between blocks of markers and phenotypic characteristics
such as disease susceptibility or response to a drug or vaccine.
Understanding, at the level of the genes, why individuals respond differently
to drugs is likely to have an impact both on drug development and on
the way in which drugs are prescribed. Drug development is a costly
process and many drugs fail in the later stages of the approval process. It is
hoped that pharmaceutical companies will be able to develop drugs more
easily using genome targets, and to target them to the groups of people
who are most likely to be able to benefit. Some drugs have failed in drug trials
because of adverse side effects experienced by some individuals; however,
these compounds may still be effective treatments in other groups of
patients. Clinical trials routinely use genetic tests to screen for variants of
the cytochrome P450 family of liver enzymes which are responsible for the
breakdown of many classes of drugs. This allows for more accurate calculation
of doses and more appropriate targeting of drugs. In the future it
should be possible for doctors to analyze a patient’s genetic profile and to
use this information to inform choices about which drug to prescribe and
also about dosage. This will reduce the risk of side effects and ensure that
the most appropriate treatment is prescribed first time. In addition to the
obvious benefits to the patient this should improve the cost effectiveness of
the treatment.
It is clear that with the advent of pharmacogenomics, diagnosis is going
to make use of a wide range of DNA-based tests. This technology is currently
most highly developed and routinely used in the area of diagnosis of
inherited disease but has many important applications in the diagnosis of
infectious disease and cancer.
As with gene therapy, it is intuitive that gene-based tests are the ideal
way in which to diagnose an inherited disorder. After all we know that the
root cause of the disorder is a genetic mutation, so detecting the presence
or absence of the mutation is an ideal approach to diagnosis. Gene-based
tests have a number of additional advantages. They can detect the presence
of disease genes in people who do not display symptoms and they can
also differentiate between different disease states with similar symptoms.
Being able to detect a disease mutation in people before they begin to display
symptoms is particularly important in cases where it is possible to
reduce the severity of the disease if intervention occurs early. A classic
example of the benefits of early intervention is in the case of phenylketonuria,
although in this case the test that is used routinely is not a genetic
one. This inherited metabolic disorder can result in toxic levels of phenylalanine
in the body resulting in mental retardation; but the disease can be
successfully managed, if detected early, by adherence to a diet with carefully
controlled levels of phenylalanine. A very successful strategy of testing
newborn babies for phenylketonuria was introduced in the UK in the 1970s
and patients suffering the adverse effects of this disorder are now rare.