Studying copy number variations using a nanofluidic platform

Qin, Jian; Jones, Robert C.; Ramakrishnan, Ramesh

Genomewide analyses have shown the existence of large numbers of CNVs in the entire human genome with large interindividual diversity (48) (49) (50) (51) (52) (53) . Many of these CNVs colocalize with genes involved in a variety of diseases or disease susceptibility and are believed to play some role in pathogenesis (54) (55) (56) (57) . The first Mendelian disorder associated with the amplification of a 750 kb DNA fragment was reported recently (54) . It appears to only be a The results of both genomic DNA and STA products are shown. The ratios of the CYP2D6 gene to the RNase P gene should be close to multiples of 0.5. The genomic ratio of 1.17 for sample NA11994 (corresponding to a diploid copy number of 2.34) reflects the partial separation of the duplication alleles in the genomic DNA. A ratio of 1.51 (diploid copy number of 3) was obtained when the sample was subjected to STA prior to the digital PCR analysis. question of time before more genetic conditions related to CNV are identified. Two standard genomewide scanning methods for CNV detection are array-based CGH and high-density SNP genotyping arrays and both were employed in the construction of the first human CNV map (58) . These microarray techniques are able to generate whole-genome CNV data and are important in CNV discovery. Their resolution is also improving with the development of new probes. However, since they are both based on hybridization, the detection of copy number changes largely depends on signal-to-noise ratio, which is sensitive to reagent and manufacturing variability. Therefore, false positive and false negative results are sometimes inevitable (59) . Additionally, the lack of standard reference genomes in the studies using these technologies further complicates the interpretation of the results (60).