Beyond genetics, there is epigenetics, elusive mover and shaker of the human genome – the poltergeist in the machine, no less.

Epigenetics is beginning to explain things that classical and molecular genetics could not. Genetic pathologist Professor David Ravine, professor of medical genetics at the University of Western Australia, says that, almost overnight, epigenetics has become a major new theme running through the biosciences, particularly human health research.

Ravine believes medical research is witnessing the dawn of a revolution comparable to the one that grew out of advances in recombinant DNA technology 25 years ago.

“The Human Genome Project gave us a catalogue of all genes in 2003, and we now know what a few of them do,” Ravine says.

“We are now able to move on and ask questions about what turns genes on and off, and regulates their activity.”

Ravine says epigenetics’ main role is in making adjustments to chromatin – the complex of DNA supercoiled around “spools” of histone proteins, that gives condensed chromosomes their compact structure. Chemical changes to histone proteins prompt chromatin remodelling, which plays a major regulatory role in gene expression.

Epigenetics is also regulated by chemical modifications to DNA. DNA can become methylated, a process in which enzymes attach methyl groups to C-G nucleotides. DNA methylation may “silence” genes by preventing the access of gene-transcription complexes.

The net effect of these changes is to regulate access of the transcription machinery to specific genomic sequences. Inaccessible genes are silent whereas accessible genes are transcribed.

“But epigenetic regulation is more than this,” Ravine says. “The rate of gene expression from the underlying genomic sequence is also influenced by microRNA and other non-coding regulatory RNAs that also act to expose or hide genes from the transcription machinery.

“Epigenetics is already providing a whole raft of new insights into the causes of disease, and with those insights will come new opportunities to test for epigenetic abnormalities in patients whose genes appear normal.

“We now know that virtually all malignancies are associated with multiple methylation abnormalities. Two mechanisms are involved – very often, cancerous cells will exhibit global hypermethylation, or specific tumour-suppressor genes will be selectively methylated, abolishing gene expression.

“Assaying for both these types of methylation defects is likely to lead to improvements in the diagnosis and treatment of cancer.”