The CNVs most difficult to genotype directly were duplications and multiallelic loci (including VNTR). They are also the categories of CNVs least likely to be tagged well by SNPs, and therefore most likely to be overlooked by linkage-disequilibrium-based association testing. The observation that VNTR are enriched among loci exhibiting high population differentiation provides evidence for the functional importance of this CNV class, which highlights the need for development of genome-wide assays for incorporating this often recalcitrant class of variants into human genetic studies.
