Also, the performance of the affinity-based assay may differ between species depending on the CpG content overall and at CpG-dense loci.
However, the SNP-dense loci on this list are likely genuine given that they are supported by multiple reads and, as discussed below, they encode gene products similar to those identified as highly polymorphic in other studies.
A BLAST-based homology analysis against the Plant Resistance Gene Database identified 32 of the 100 most SNP-dense loci as putative R genes (http://prgdb.crg.eu/wiki/Main_Page) [ 31].
Notably, the distal enhancer of Oct4 represents the densest binding locus for the key pluripotency-specific transcription factors in ESCs (Chen et al., 2008), which makes it an ideal reporter for tracing the course of changes during the establishment of ESCs from ICM.
Unexpected GWAS findings were another focus: the first generation of GWASs did not show the expected 'Manhattan skyline' of dense signals, and loci reported by GWASs so far explain only a small proportion of the observed phenotypic variation.
While the healthy cells revealed mainly CpG dense, highly hypomethylated loci and some CpG poorer regions with moderate hypomethylation, the ICF patient presents CpG poor regions with low to intermediate DNA methylation levels (Fig. 2E and F).
Because the removal of deleterious mutations by natural selection also reduces within-species genetic diversity within functional loci, dense population genetic data have the potential to reveal genomic elements that are currently functional.
Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci.
These findings imply that bisulfite sequencing data should be interpreted with caution, since loci containing dense regions of hydroxymethylated DNA might be incorrectly assumed to contain methylated CpGs, and might also be underrepresented in quantitative analyses of DNA methylation status.
These investigations used multiple loci and dense geographic sampling to uncover cryptic genetic subdivisions.
