Table 1

Attributes that can be used to define positional candidacy

Attribute type

Attribute

Questions to be asked of each regional gene

Transcriptional

Expression state

Which genes are expressed in tissues relevant to the disease of interest?

Which genes show restricted or preferential expression in relevant tissues?

Which genes show expression within organelles (such as mitochondria) implicated in disease etiology?

Differential expression

Which genes show robust expression differences in comparison of pertinent tissues from 'disease' versus 'control'?

Which genes show robust expression differences in response to relevant environmental, pharmacological or physiological manipulation?

Coregulation

Which genes appear to be coregulated with members of other pathways implicated in disease?

Proteomics

Protein expression

Which genes code for proteins that show differences in expression and/or post-translational modification in diseased tissues, or response to relevant manipulation?

Interaction

Which genes code for proteins known to interact with other proteins implicated in disease etiology?

Function

Which genes code for products that have functional (such as ion channels) or localization (for example, membrane proteins) properties that are pertinent to disease etiology?

Metabonomics

Biomarkers of disease

Which genes code for proteins involved in regulation of metabolic pathways implicated in disease through metabonomic comparisons?

Pathway analysis

Which genes code for products involved in pathways implicated in disease?

Comparative analysis

Homologies

Which genes have homologies (or other relationships) to genes implicated in equivalent phenotypes in other animals?

Ortholog mapping

Which genes are members of gene families for which other members are implicated in the disease or related diseases?

Which genes are members of gene families for which other members map to other regions of linkage containing as yet unidentified susceptibility genes?

McCarthy et al. Genome Biology 2003 4:119   doi:10.1186/gb-2003-4-10-119