Identifying gene SNPs
Dr Jonathan Kerr
Investigator
Dr Jonathan Kerr
Institution
St George’s Hospital, University of London, London, UK
Background and aims
The information inherited from our parents (usually in the form of a gene, a sequence of DNA) has to be translated into a product, such as an RNA molecule or a protein, before it can be used by the body, a process called gene expression. In recent years, the number of scientific reports investigating gene expression in ME/CFS has increased steadily, and the genes found to be over or underexpressed seem to be related to ‘immunity and defence’, supporting what is known about the role of the immune system.
Dr Jonathan Kerr’s group has been one of the most active in defining the molecular basis of ME/CFS. Their initial study of gene expression in patients demonstrated marked human gene dysregulation, principally affecting the immune system. And in 2007, the latest in a series of papers was published in the Journal of Clinical Pathology outlining the identification of a putative ‘gene signature’ for the illness consisting of 88 human genes.
These genes can be subdivided into categories by diseases and disorders, say, or by molecular and cellular functions. The research team says that three of the genes identified are directly linked with mitochondrial metabolism, and a further ten have indirect links with mitochondrial metabolism.
As these 88 genes have been linked directly to the pathogenesis of ME/CFS, the next step is to study the inherited determinants of susceptibility by examining single nucleotide polymorphisms (SNPs) — pronounced ‘snips’ — within these genes. Some SNPs have been linked with features and complications which might be associated with ME/CFS (e.g., IL10RA SNPs are associated with lymphoma, a disease which some have speculated occurs more frequently in ME/CFS).
With funding from ME Research UK, the St George’s group will shortly begin the next phase of their work: identifying the key SNPs for each of these 88 genes. As there are hundreds of SNPs within each gene, the team proposes to focus on ‘determinative’ SNPs (i.e., those which are known to predict all or most of the others within one gene); there are typically 3 to 7 per gene. Once these have been identified, the researchers will design and use low density array cards to test genomic DNA samples of 105 patients in the initial sample group. After comparing allele frequencies between the ME/CFS and control groups, the allele frequencies will be related to the gene expression levels.
The results will indicate those genes within the 88-gene ‘signature’ for which inherited determinants exist, and provide a thorough genomic database from which to determine the role that these SNPs may play in the pathogenesis of ME/CFS.
