CNV inheritance patterns. To determine whether a CNV may be inherited or is a de novo event, trios including child, mother, and father are assessed. Currently, there is the potential for erroneous interpretation of the trio data since array-based CGH assays calculate copy number additively. For example, a mother who has a one-copy CNV on one chromosome and a three-copy CNV on the homologous chromosome (i.e., four total copies) would have no copy number difference when compared with a reference individual with four total copies (i.e., two copies on each homologous chromosome). In addition, a father who has two copies present on each homologous chromosome (i.e., four total copies) would also have no copy number difference when compared with the reference individual. If the child inherits the maternal chromosome containing three copies and the paternal chromosome containing two copies of the CNV, the child ends up with a total of five copies of the CNV. Upon comparison with the reference, the child could appear to have a de novo CNV. The development of locus-specific and allele-specific quantitative assays will aid in the interpretation of these CNV inheritance patterns.
