Copy-number-variation and copy-number-alteration region detection by cumulative plots

Regions with copy number variations (in germline cells) or copy number alteration (in somatic cells) are of great interest for human disease gene mapping and cancer studies. They represent a new type of mutation and are larger-scaled than the single nucleotide polymorphisms. Using genotyping microarray for copy number variation detection has become standard, and there is a need for improving analysis methods.

We apply the cumulative plot to the detection of regions with copy number variation/alteration, on samples taken from a chronic lymphocytic leukemia patient. Two sets of whole-genome genotyping of 317 k single nucleotide polymorphisms, one from the normal cell and another from the cancer cell, are analyzed. We demonstrate the utility of cumulative plot in detecting a 9 Mb (9 x 10(6) bases) hemizygous deletion and 1 Mb homozygous deletion on chromosome 13. We also show the possibility to detect smaller copy number variation/alteration regions below the 100 kb range.

As a graphic tool, the cumulative plot is an intuitive and a scale-free (window-less) way for detecting copy number variation/alteration regions, especially when such regions are small.