detections,19,20 the first wave of GWAS has largely missed the contribution of CNVs. This occurs because CNVs are not easily tagged by SNPs (influencing Hardy-Weinberg Equilibrium and thus being eliminated during genotype quality-control checks), CNVs might have a wide range of copy number variability, and often fall in genomic regions not well covered by genotyping platforms or not genotyped by the HapMap project.21 Recently developed genotyping chips allow the simultaneous interrogation of SNPs and CNVs across the genome with improved coverage.22 The genome-wide detection of rare CNVs, as well as the discrimination capacity for variants with wide range of variability in copy number, represent important challenges for genotyping technology research. Since the global inventory of CNVs remains incomplete, and with limited empirical data currently available, the extent to which current arrays capture the structural variome and enable a more comprehensive elucidation of the spectrum of genomic variability remains unclear.18,21 Even under optimal desgin, genome-wide SNP screens will still not be informative about the role of other components of the regulatory architecture of the genome, such as noncoding RNAs or epigenetic modifications (somatically-acquired or trans-generationally inherited); complementary techniques, such as high-throughput methylome analysis, will be ultimately needed.23,24
