26.1 Infectious Diseases

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approach less reliable. Microarrays are extensively applied to this task, as well as a

related approach in which the oligonucleotides are attached to small microspheres

(beads) a few micrometres in diameter. In effect, each bead corresponds to one spot

on a microarray. The beads are individually tagged (e.g., using a combination of a

small number of different attached fluorophores, or via the ratio of two fluorophores).

Several hundred different types of beads can be mixed and discriminated at the current

level of the technology. A major difficulty in the use of binding assays (hybridization)

based on gene chips or beads for allele detection is the lack of complete discrimination

between completely matched and slightly mismatched sequences. An alternative

approach is based on the very high sequence specificity of certain enzyme reactions,

such as restriction.

As well as trying to identify genes, or gene variants, responsible for disease

by analysing the genomes of patients, gene segments can be cloned into cells and

examined for disease-like symptoms (including the pattern of expression of certain

proteins). This approach is called functional cloning.

Although much effort goes into understanding the correlation between gene asso-

ciation and disease, the rather limited success of attempts to correlate groups of

SNPs with particular diseases suggests that there are many diseases enabled by com-

binations of two or more variant genes. The problem of correlation then acquires a

combinatorial aspect and it becomes much more difficult to solve.

26.1

Infectious Diseases

It may well be that the impact of genetic knowledge acquired through bioinformatics

will have an earlier impact on microbial infections than on intrinsic genetic disorders.

It is a straightforward application of bioinformatics to design minimal microchips for

the unambiguous diagnosis of a microbial infection from traces of DNA found in the

blood of the patient. ⁹ The special aspects of diagnosing rapidly mutating variants of a

virus during a pandemic are discussed in Chap. 29. Sequencing the entire microbiome

would doubtless be of immense value in diagnosing disorders of the gastrointestinal

tract (GIT), which can lead to general ill health, but considering that the genome of

the gut flora is some two hundredfold bigger than that of the human genome proper, ¹⁰

this is still a challenge. Furthermore, the relative tractability of prokaryotic genomes

will hopefully lead to an increased understanding of the nature of symbiosis. Given

the ubiquity of microörganisms everywhere in our environment, symbiosis might

well be considered a rather general phenomenon. The challenge is to understand

multimicrobial ecosystems and how benign coexistence can sometimes suddenly

become life-threatening to host metazoans.

9 Chumakov et al. (2005).

10 There are about ten times more cells in the human microbiome than in the human body proper (cf.

Chap. 19), but of course these cells are very small (and their individual genomes are much smaller

than that of the human being) and their total mass only amounts to some 2% of human body mass.

There is, however, an enormous variety of different microörganisms in the GIT.