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Genetic factors have a well established role in the aetiology of inflammatory bowel disease (IBD). The mode of inheritance suggests a polygenic disease with penetrance of the genetic factors being strongly influenced by the lifestyle of an industrialised society. The development of linkage analysis has allowed the generation of important molecular clues to the location of putative disease genes.1
The inheritance of genomic DNA can be traced by identification of highly polymorphic regions (“microsatellites”). Ideally, polymorphic regions should be used which are present in a high number of variations (“alleles”) in the population (that is, are highly informative).
If a phenotype (for example, disease) is inherited, the use of linkage analysis assumes that it will be possible to trace the piece of DNA which contains the putative disease gene. In affected relative pairs of individuals (sharing the same phenotype), certain areas of the DNA which contain disease genes should therefore be coinherited more frequently in comparison with random distribution. In a systematic analysis (“genome scan”), a densely spaced set of microsatellites is used throughout the entire genome to identify the origin of DNA and follow them through the inheritance process. Statistical measures can be used to qualify the degree of over proportional sharing (of polymorphic alleles). This “LOD” score (which roughly corresponds to a logarithmised p value) is usually displayed as a function of the genomic map (for example, fig …
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- Inflammation and inflammatory bowel disease