Editorial
Diagnostic Molecular Biology
John Beilby1,2
1
PathWest, QEII Medical Centre, Clinical Biochemistry, Nedlands, Western Australia 6009
2
Royal Perth Hospital, Biochemistry Department, Perth, WA 6001, Australia.
For correspondence: Dr John Beilby e-mail: John.Beilby@health.wa.gov.au
Diagnostic molecular biology is arguably the fastest growing
area of laboratory medicine and has the potential for a
major impact on clinical medicine within the next decade.
As this area develops, so will our understanding of how
structural variations in DNA and RNA are associated with
the development of chronic diseases. New technologies
have contributed to the dramatic acceleration in our capacity
to investigate the genetic components of disease. Future
developments in this area will be fuelled by improvements in
technology and the availability of large, carefully documented
study populations.
Many genes responsible for monogenic diseases have been
successfully isolated and are used for the clinical diagnosis of
disease, identification of gene carriers or predictive testing of
subjects who may develop certain diseases. Genes that cause
complex diseases, such as cardiovascular disease, asthma and
osteoporosis are being studied but it will take time before the
use of these genetic risk factors are used in clinical practice
due to the complexity of the interactions between genetic and
environmental risk factors.
Diagnostic molecular biology is widely used in a number of
areas including haematology, immunology and microbiology
with possibly the least developed area being clinical
biochemistry. Apart from diseases such as cystic fibrosis and
genetic haemochromatosis, most genetic diseases tested for
in clinical biochemistry laboratories are rare in the general
population. However, molecular methods will be increasingly
incorporated into all areas of pathology, not to replace current
tests but as an aid in evaluating the future risk of disease.
In this issue of the Clinical Biochemist Reviews a series of
manuscripts have been selected that highlight a snapshot of
the 'state-of-art' of diagnostic molecular biology testing in
clinical laboratory medicine.
The opening article by Siah et al. provides a comprehensive
review of iron metabolism and pathophysiology of iron
overload. The identification of the HFE gene by Feder et
al. in 1996 was a major step forward in understanding iron
metabolism and has provided considerable impetus to the
study of iron metabolism. Genotyping for the common variants
of the HFE gene is the most requested genetic test performed
in clinical medicine. Possibly because it was the first genetic
test to be listed for reimbursement on the Medicare Benefit
Schedule for patients with an elevated transferrin saturation or
serum ferritin; or for a patient who has a first degree relative
with haemochromatosis or a relative with homozygosity for the
C282Y genetic mutation, or compound heterozygosity (www.
medicareaustralia.gov.au). In 2004/05 there were 39,404 HFE
tests claimed through Medicare at a cost of $1,257,832.
Pharmacogenomics is the study of the effect of genetic
variations on drug response, efficacy, and metabolism. This
area has the potential to be one of the first large-scale clinical
applications of diagnostic molecular biology. It is certain to
have an enormous impact on the practice of clinical medicine
by deciding on the most effective choice of drugs and avoiding
their potentially dangerous side effects. However, to-date
there are very few examples of polymorphisms that have a
clinically relevant effect on drug response. It is likely that drug
response will be complex, influenced by the environment and
multiple genetic factors. In the second article in this issue, Dr
Jan van der Weide and Dr John Hinrichs from the Department
of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The
Netherlands discuss the role of pharmacogenomics on the
metabolism of antipsychotic and antidepressant drugs. They
note that in their psychiatric clinic, TDM and genotyping
for CYPD6 and CYP2C19 polymorphisms are routinely
performed for all hospitalised patients, whereas in Australasian
laboratories these tests are almost never performed in routine
clinical practice.
Clin Biochem Rev Vol 27 February 2006 I 3
Petersen
Beilby J H
The third and fourth articles in this collection cover areas that
are not associated with clinical biochemistry but are commonly
studied in clinical medicine. The article on the diagnosis
of haemoglobinopathies by Professor Ron Trent covers an
important and growing area for the application of molecular
biology techniques in Australasia. Haemoglobinopathies are
the commonest genetic defect worldwide with an estimated
269 million people who are carriers. The author reviews the
area and provides a three-tier approach for the diagnosis of
haemoglobinopathies. In the next article Dr David Speers
discusses how molecular biological methods for the detection
and characterisation of microorganisms have revolutionised
diagnostic microbiology with the rapid diagnosis of
microorganisms of public health importance. Treatment of
certain microorganisms has been improved by viral resistance
detection and viral load testing for the monitoring of responses
to antiviral therapies.
The fifth manuscript by Dr Kristine Barlow-Stewart and
Professor Leslie Burnett covers the ethical issues associated
with the use of DNA testing. This paper discusses the ethical
implication of many of the recent advances in genetics and
highlights some of the still unresolved issues. As clinical
biochemists, we have always dealt with ethical issues relating
to biochemistry results. However, as the authors point out,
we need to better understand the shared nature of genetic
4 I Clin Biochem Rev Vol 27 February 2006
information within families, and the greater sensitivity and
privacy issues associated with genetic information.
The final manuscript by Dr Cyril Mamotte provides a
comprehensive overview of the modern techniques used for
the detection of polymorphisms in DNA. The revolution we are
experiencing within the area of genetics is technology driven.
As newer and more cost efficient techniques are developed to
study the structure of DNA, the area will develop at an even
faster rate.
As clinical biochemists, we are working in a unique period of
time where DNA technology is developing quickly and the
potential importance of the area is widely recognised. We have
the opportunity to help develop evidence for the usefulness of
DNA testing to assist with the diagnosis of chronic diseases,
and hopefully improve the health of the community.
The manuscripts compiled in this issue are a fair representation
of the current uses of diagnostic molecular biology in clinical
laboratory medicine. Diagnostic molecular pathology will
become a greater part of routine clinical biochemistry in
the future, but only when it can be applied as a risk factor
(predictor) for the common complex diseases. At the present it
is not possible to say how long this will take, but I am certain
it will happen.