Haplotypes and the systematic analysis of genetic variation in genes and genomes

'Haplotypes' have been used in various fields of genetics for a long time, in a variety of contexts, and for different purposes. Now, haplotype-based approaches to the analysis of candidate genes and genome-wide linkage disequilibrium (LD) mapping have gained center stage. It is time to explicitly distinguish the different concepts implied in the present 'haplotype' approaches: 'haplotypes' are not 'haplotypes', after all. The distinction of three different categories, 'ancestral, common haplotypes' or 'haplotype blocks', 'gene-based haplotypes as complex genetic markers' and 'gene-based functional haplotypes', is proposed. These categories serve as framework to review and analyze in particular the recent work suggesting evidence for a haplotype block structure of the human genome and the body of comparative sequencing studies addressing haplotype and LD structures at the gene level. Haplotype approaches will be evaluated along the dimensions 'preselection of variants versus complete DNA sequence information', 'role of LD' and 'stages in the process of disease gene identification'. Overall, the 'content' of 'haplotypes' is conceived as a function of available technologies to evaluate genetic variation and general advances in human genome research.