 |
| The figure shows number of publications per year identified with the search terms “genetic linkage”, “candidate gene”, “genome wide |
| association study”, and “next generation sequencing” according to PUBMED as of March 2011. The figure shows linkage studies |
| appear to have peaked and are now in decline, while the term candidate gene is still in common usage, although it now typically |
| refers to any gene identified as a plausible cause of disease however identified rather than as a type of study in its own right. The term |
| “genome wide association study” has the steepest gradient indicating a rapid reporting of findings using this technique, and next |
| generation sequencing is too new a term to have really made an impact on the literature yet. |
| Genetic Linkage. A technique which examines genetic variants through multiple generations of the same family and examines |
| incidence with disease status. A powerful technique for Mendelian diseases where a single gene controls the phenotype, genetic |
| linkage has had relatively little success in ischaemic stroke due to the late age of onset and lack of large pedigrees with multiple |
| affected individuals available for meaningful study. |
| Candidate Gene Study. A gene hypothesised to be involved in or a risk factor for any disease with a genetic basis. Originally |
| candidate gene study referred to a specific type of study whereby genes were typically identified on the basis of biological plausibility |
| for the disease in question and then examined single for genetic variants at that one locus in a so called hypothesis driven manner. |
| More recently the advent of candidate gene has evolved to include any gene identified from range of genetic investigations rather |
| than referring to a particular type of study specifically. Its usage in the literature is commonplace and maintained for this reason. |
| Genome Wide Association Study. A technique which looks at multiple genetic variants, typically between 300,000 and 1 million at |
| a time in a single experiment, in a nonhypothesis driven manner. The variants are spread throughout the genome at random |
| and allows systematic investigation of a large number of regions in cases and controls. The technique relies on association of specific |
| alleles with disease state. Unlike genetic linkage, individuals are not related, thus requiring large, typically several thousand, cases |
| and controls for comparison. Although complex and expensive, this technique has identified more loci than any other for common |
| polygenic disease under the Common Variant Common Disease (CVCD) hypothesis. |
| Next Generation Sequencing. Defined as next generation since it uses the same array based format as genome-wide association arrays |
| rather than more traditional liquid based Sanger sequencing, NGS is currently the cutting edge technology available for direct |
| sequencing of DNA. Allowing determination of the entire exome (coding portion) of the human genome in a single experiment, |
| NGS is being used to examine the Rare Variant, Common Disease (RVCD) hypothesis. Although expensive, since it relies on the |
| identification of rare variants far fewer individuals are required for studies. Current advances in multiplexing of samples by labeling |
| with genetic tags before sequencing allows mixing of samples and a reduction in cost. |
