Figure 1

Potential recombination sites within a linkage disequilibrium (LD) block. Patterns of LD for the complete major histocompatibility complex were obtained for a panel of 180 Centre d'Etude du Polymorphisme Humain founder chromosomes [16] and LD-blocks defined according to Gabriel et al. criteria [19] employing Haploview [32]. (A) The region selected for the analysis constitutes an LD-block extending over a ~110 kilobase (kb) DNA segment (National Center for Biotechnology Information built 35 coordinates: 32321766-32431723) containing most of the C6ORF10 gene, with an average space between single nucleotide polymorphisms (SNPs) of 1.6 kb. This region also represents a recombination cold spot -- with recombination rates = 0.00931 centimorgans/megabase, ten times lower relative to that on the neighbouring area -- surrounded by two recombination hot spots identified in NOTCH4 and C6ORF10 genes [16]. (B) Ten haplotypes (rows) observed in this sample, which were recognised based on alleles at 68 variable positions (SNPs, in columns) within the selected LD-block. Haplotype names and frequencies (per cent) are given on the left. (C) A break in the haplotype alignment suggesting the presence of ancestral recombination within the LD-block. Haplotypes were then split at a potential recombination site into two sub-regions (with 41 and 27 SNPs, respectively) aiming to construct a phylogenetic network in order to check for consistency. (D) The distribution of variation among haplotypes as represented by median-joining trees obtained for both sub-regions employing the NETWORK program [33]. Haplotypes F and D are grouped closely related within each network but belong to different clusters when comparing networks from the two sub-regions. The number of substitutions involved in these branching differences could preferably be explained by recombination events rather than owing to mutations occurring between haplotypes. The distribution pattern of these differences adds consistency to this view and strongly suggests the presence of recombination. The circle size is proportional to the haplotype frequency, and the number of substitutions between nodes is represented by the number of lines between them. The site where the haplotypes were split can be changed to few positions on either side of the current site without significantly modifying the topology of the network.