Sensitive quantification of mosaicism using high density SNP arrays and the cumulative distribution function

Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Function as applied to single nucleotide polymorphism (SNP) array data, to quantify somatic mosaicism throughout the genome. We also demonstrate application of the method to novel diseases and mechanisms.

► Quantifying mosaicism using SNP chips and the cumulative distribution function. ► Detection of full and partial chromosomal mosaicism missed by other techniques. ► Identification of a new disease mechanism: graded loss of single telomeres.