Candidate gene approaches

The use of mouse models to look at the effects of individual genes on incubation time have proved very useful in confirming the role of proteins that have been implicated in prion disease from a range of different studies. Prion diseases are characterised by the absence of a classical inflammatory response however, atypical inflammation characterised by microglial activation is central and precedes neuronal death. Consequently, a number of pro- and anti-inflammatory cytokines and chemokines have been investigated. 

A straightforward approach to in vivo hypothesis testing is to generate a knockout mouse for the gene of interest, inoculate with prions and look at the effect on incubation time as compared to wild type controls. Experiments of this nature have been carried out for the anti-inflammatory cytokines interleukin-4 (114), 1110 and 1113 and the chemokine, monocyte chemoattractant protein-1 (Mcpl) [82, 83]. Following intracerebral inoculation with the RML strain of mouse adapted scrapie, no significant differences were seen for mice deficient in either 114,1113 or both. However, for mice 

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The candidate gene approach directly tests the association of selected genes with drug response or ADR. The major sources of candidates which code for receptor, enzyme or ADME targets, are obtained through literature surveys. Most pharma-... 

E. The Candidate Gene Approach for Identifying Risk Genes... 

These studies clearly showed how, by a carefully designed candidate gene approach combined with functional studies, one can gain important insights into not only the functional relevance but also into the possible molecular mechanism of pharmacog-enomic associations. 

Huh JH, Kan BC, Nahm SH, Kim S, Ha KS, Lee MH, Kim BD (2001) A candidate gene approach identified phytoene synthase as the locus for mature fruit color in red pepper Capsicum spp.). Theor Appl Genet 102 524-530... 

In the candidate-gene approach - the most frequently used approach adopted to identify the predisposing or causal genes in the complex and multigenic and multifactorial diseases - genes with a known or proposed function, with the potential to influence the disease phenot)q)e, are investigated for a direct role in disease. In a small number of cases of t)q)e 2 diabetes, candidate-gene studies have identified mutations in. 

Simko, L, Costanzo, C., Haynes, K. G., Christ, B. J., Jones, R. W. (2004a). Linkage disequilibrium mapping of a Verticillium dahliae resistanee quantitative trait locus in tetraploid potato (Solanum tuberosum) through a candidate gene approach. Theoretical and Applied Genetics, 108,2X1-224. 

Introduction Candidate Gene Approach Pathway-Based Approach Genome-Wide Scanning Approach... 

Besides the examples listed above, there are numerous exploratory association studies that have identified many potential polymorphism biomarkers for treatment response in membrane transporter, drug-metabolizing enzyme, and drug target genes. The methodology and statistical analysis for the candidate gene approach are simple the results are easy to interpret. 

Higher predictive power than candidate gene approach taking consideration of gene-gene interactions in polygenic traits... 

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