ABSTRACT
Summary .................................................................................................................. 55 5.1 Introduction .................................................................................................... 56 5.2 High-Resolution Mapping.............................................................................. 56
5.2.1 Congenic Strains and Substrains ....................................................... 56 5.2.2 Alternative Strategies ......................................................................... 59
5.3 Positional Cloning.......................................................................................... 62 5.3.1 Pure Positional Cloning ..................................................................... 63 5.3.2 Positional Candidate Approach ......................................................... 65
5.3.2.1 Mapping of Candidate Genes in the QTL ......................... 65 5.3.2.2 Combining QTL Mapping and Expression Profiling ........ 66 5.3.2.3 Haplotype Mapping ............................................................ 66
5.4 Conclusion...................................................................................................... 67 References................................................................................................................ 67
Although quantitative trait loci (QTL) mapping analysis has become very popular, the final goal to positionally clone and identify the relevant gene(s) remains difficult for the genetic dissection of complex traits. This chapter reviews the different approaches that have been used thus far. First, various breeding strategies and haplotype mapping have been developed in order to narrow down the QTL interval. Once high resolution mapping of the QTL is achieved, positional cloning of the relevant gene can be performed. Until a few years ago, a contig of DNA clones covering the QTL interval was constructed and several techniques were used in order to extract the coding sequences of the contig. This is now obsolete in human, mouse and rat species for which genomes are sequenced. Progress in genome annotation and techniques based on microarrays gene expression analysis are used to pull out candidate genes from the fine-mapped QTL interval. Finally, sequence analysis provides candidate mutations that then need to be validated by functional studies.
