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Gene Mapping
Dr Melody Caramins
BMed PhD FRCPA FFSc (RCPA)
Genetic Pathologist
Gene mapping is a general term for discovering the genetic basis for a disease.
The human genome (all the genetic code for an individual) consists of
approximately 2 ‘sets’ of 3 billion letters, A, C, G, and T; one set from each
parent. One of the aims of the Human Genome Project was to develop the
techniques and technologies used for gene mapping, and indeed these have
changed considerably over the years. When the project started, their ambitious
aim was to sequence, or read, the entire genetic material from a human individual.
This cost approximately USD 3 billion, and took about 15 years. Now, the entire
human genome can be sequenced for approximately USD 5,000 and would
take days to weeks, rather than years. For the same cost as the original human
genome, you can now sequence the entire genome of over 20,000 individuals.
Chromosome studies (karyotype)
Exome sequencing
Sequencing a
panel of genes
Chromosome microarray
Simple gene test
There are many ways of discovering the
genetic basis of a disease, ranging from
simple to complex. Imagine taking a
landscape picture with a digital camera; you
could use all the pixels to take a very clear
picture of a tree, or a low resolution picture
of the whole landscape, or you can buy a
better camera and take a high resolution
picture of the entire view.
techniques. To use the picture analogy, you
might just see a smear of green and blue in
a landscape.
These days, your doctor may choose to
undertake a chromosome microarray,
which looks for small bits of extra
(duplicated) or missing (deleted) genetic
material over the entire genome and
provides more information than previously.
This would be like taking a lower resolution
picture of the whole landscape. You would
see the main features of the landscape,
such as trees, some hills, the sky and
some clouds; but you might miss some of
very fine details of the birds and the grass.
At the simple end, if you saw your doctor,
and there was a concern about a specific
disease, then they could order a genetic
test to determine whether you do in fact
have a genetic variant in a gene that might
cause the disease, or predispose to the
disease. This would be like taking a very
clear picture of a tree in the landscape.
Finally, at the most complex end of genetic
testing, is sequencing all of the known
genes, or alternatively, sequencing the
entirety of the genome.
A slightly more complicated scenario is
where you might have a condition, like
hereditary deafness, where many genes
could be involved. There are literally
hundreds of genes (~400) that can cause
hereditary deafness. Until recently, you
would have to test these by sequencing
them one by one; a daunting task. With
the newer sequencing technologies, this
could be achieved in a matter of weeks.
Sequencing all of the known genes is
also known as exome sequencing, which
consists of sequencing ~2% of our entire
genetic material. Exome sequencing
is transitioning from a research test
to a diagnostic test. Although no labs
in Australia currently offer it routinely
for diagnosis, it is anticipated it will be
available more routinely in the next year.
The exact cost is difficult to anticipate
accurately, but would be expected to be
$1000 - $2000, with no Medicare rebate
currently available for this test. This would
be like taking a pretty clear picture of the
whole landscape. But you might end up
seeing some things that you might not
For something even more complicated,
you might have a scenario where you have
a child with developmental delay, where a
genetic cause might be suspected. Some
years ago, this test was done by examining
all the chromosomes under a microscope,
at 50 times less resolution and thus
with much less information than current
recognise if you had never been used to
seeing this level of detail. About 1-3% of
exome sequencing tests identify variants
which were unexpected, and more whose
effects cannot be completely predicted.
Only about 4,000 of the 23,000 genes
in the genome have been connected to
a particular disease or diseases, and the
genetic basis for some common illnesses
such as heart disease and diabetes remain
largely unknown, although much progress
has been made with various cancers.
Sequencing all of the genetic material, or
whole genome sequencing, is the most
complex genetic test and is currently only
undertaken in a research setting due to the
cost and difficulty of interpretation.
Given that our knowledge of genetics is
evolving very rapidly, if you could have your
genome sequenced, the interpretation of
the report you would receive now would
more than likely change over time. As
new information becomes available, that
report might need to be updated, based on
information that becomes available in the
years to come.
Gene mapping is a colloquial term; these
days it is generally understood to refer to
a test which looks at many genes at the
same time – usually by exome or genome
sequencing, or by chromosomal microarray
testing. These tests all look at your genome
at different levels of resolution. Which kind
of picture is necessary will depend on what
you need to see.
Dr Melody Caramins BMed PhD FRCPA FFSc (RCPA), Genetic Pathologist
Dr Melody Caramins is a genetic pathologist and a conjoint senior lecturer at the University of New South Wales. She is head
genetic pathologist at QML Pathology and national head of genetics at Specialist Diagnostic Services. She has extensive
experience with complex and simple genetic testing and has undertaken gene mapping research. Her research on gene
mapping has been published in some of the leading genetics scientific journals.
Specialist Diagnostic Services Pty Ltd (ACN 007 190 043) t/a QML Pathology
PUB/MR/1195, version 1 (May-14)