Humans

There is enormous potential for the use of this technique in human medicine. Many of the uses of DNA microarrays concerned with humans are comparisons: comparing the gene expression associated with one phenotype with the gene expression associated with another. A particular benefit of this technology is that it can rapidly provide information about the genetic basis of disease.

An example of this is the use of DNA microarrays to study the gene expression characteristics of the 2 inflammatory diseases rheumatoid arthritis and inflammatory bowel disease.

Here Heller et al. conducted an experiment where probes were produced from arthritic tissue and IBD mucosa and labelled with either Cyt 3 or 5 fluors. These were then exposed to a microarray of cDNA targets from genes known to be involved in the disease processes. This study revealed the genes involved in the processes, newly discovered and previously known, and also looked at the differential expression between the 2 disease states.

Another specific example of the application of this technique in human medicine is in the study of tumours.

Golub et al. describe some of the problems involved in treating cancer. There has been an improvement in the classification of cancers , but there still remains no clear way to identify new classes of cancer - known as class discovery - or to assign tumours to classes already described - known as class prediction.
It is possible that the use of DNA microarray technology will help solve some of these problems. Traditionally, cancers are classified mainly on the morphological appearance of the tumour. However there are considerable problems with this, including the fact that tumours that are morphologically similar often follow very diverse clinical courses. A more systematic approach to cancer classification is greatly needed, and this could be provided by DNA microarrays: the technique can be used to monitor the expression of thousands of genes simultaneously. The results of Golub et al.'s experiment illustrate this possibility.

Alizadeh et al. have described this use of gene expression monitoring, by microarrays, in diffuse large B-cell lymphomas - the most common type of non-Hodgkin's lymphoma. With this disease 40% of sufferers respond well to the treatment, but 60% of cases are fatal. This clinical heterogeneity implies a molecular heterogeneity in the tumours. DNA microarrays were used to characterise the tumours, and revealed that the two sub-groups of the disease should in fact be considered as separate diseases. This investigation proves the usefulness of DNA microarrays in this field.

DeRisi et al. showed that DNA microarray technology can provide valuable information about the molecular pathology of particular tumours. In this experiment the tumourigenic properties of the human melanoma cell line UACC-903 were investigated.

Perou et al. used cDNA microarrays and a clustering algorithm to study the patterns of gene expression in human mammalian epithelial cells. These cells were studied both in primary human breast tumours, and in culture.
The results from this experiment show that this technique is both possible and useful to study differences in the gene expression patterns in human cancers. The results show that this technique is useful in classifying tumours.

Loftus et al. used cDNA microarrays in the study of gene expression in neural crest melanocytes.
This study made use of the large amount of sequence information available in the dbEST (Expression Sequence Tag database). From this they identified a neural crest-derived melanocyte cDNA set appropriate for the microarray analysis. In doing this, the experiment showed the advantages of selecting appropriate cDNAs that it is possible to use, in order to study gene expression profiles.

cDNA microarrays have also been used in the study of particular cellular process, for example adipogenesis:

Zhou et al. used cDNA microarrays to look at gene expression during adipogenesis. The microarrays in this experiment contained over 5,000 cDNAs clones.
The results showed that 33 genes, including 28 known ESTs and 4 with no homologies identified, have a level of expression that differed by over 250%. These results agreed with those obtained by Northern blotting.

As described in Problems, DNA microarray technology can be used in pre-natal screening.

This will have a number of benefits, including the identification of disposition to many diseases, including cancer and mental illness such as schizophrenia.
However, it will also enable the identification of the presence of certain traits that are considered 'desirable'. This has a number of ethical implications.

As well as pre-natal testing, DNA microarray technology will enable neonatal testing.

As described by Dobrowolski et al., the new methods of using DNA microarray technology have brought decreases in the cost of the technique. This will allow an increase in use, for example more widely applied population screening.

One example of this screening is of newborn babies - it is possible DNA microarrays could be used to screen for a number of treatable disorders, such as sickle cell disease. This could be done using small blood samples taken from babies.

This will have a number of benefits, allowing immediate disease identification and therefore early treatment.


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