However, these blocks are separated by recombination hotspots which lead to "switching" of the blocks and hence the Battenberg pattern illustrated in Figure 2 A (chromosome 7).
As previously reported [32], we observed two regions of high linkage disequilirium (LD) separated by a recombination "hotspot" within MEFV intron 2 (Figure 2).
The most novel association in the model is with the SNP rs9277535 in the class II gene HLA-DPB1, centromeric of the DR/DQ region and separated by a recombination hotspot.
A second independent marker, rs6983267, was identified by GWAS with replication; though the two markers lie in contiguous blocks of LD, they are separated by a recombination hotspot (Yeager et al. 2007).
Then a second independent variant, rs11649743, located at chromosome 17q12 and separated by a recombination hotspot from the first variant, was subsequently found to be associated with risk [ 26].
This might lead to perception becoming trapped between one or more reversal hotspots, separated by a fixed angle of rotation e.g. by 180° in the case of the sloping gables.
Since recombination in X-linked and autosomal portions of the human genome is often concentrated in hotspots separated by DNA regions with little or no recombination [44], [45], we felt that our choice of high LD genomic regions (precisely D'>0.7) in our samples would be the most informative.
rs706793 (chr12:48,754,036) and rs11169552 (chr12:49,441,930) are separated by a predicted recombination hotspot at ∼48.8 Mb in the HapMap data (Fig. 3) but not in our own data (Fig. 5), although LD in the region is complex (Supplementary Material, Fig. S1).
Adjacent blocks are separated by sites that show evidence of historical recombination (hotspot).
Recent evidence has shown, however, that meiotic recombination events predominantly occur in narrow hotspots of 1 2.5 kilo bases (kb) separated by as much as 50 100 kb of DNA that very seldom recombines [ 41- 44].
