Supplementary Figure 1. Derived duplications and deletions versus duplications and
deletions relative to a reference genome. a) A duplication detected relative to a reference
genome may in fact be a deletion allele of previously duplicated sequence, with the
reference genome having the deletion allele. Note that for this to be the case, the
duplication must have been recent enough for DNA from both copies present in a sample
lacking the deletion allele to exhibit hybridization to the set of probes corresponding to
the single copy present in the reference genome. This implies that apparent duplications
that are actually deletions of duplicated sequences will rarely be detected unless certain
regions of the genome have high enough mutations rates for recent duplicates to have an
appreciable chance of being deleted. b) A deletion of previously duplicated sequence
detected relative to a reference genome may in fact be a duplication present in the
reference genome but not in all samples. Note that these will only be detected when the
duplicates are dissimilar enough to be probed separately. Thus, cases like the bottom of
panel b) will likely rarely be detected.
Supplementary Figure 2. Allele frequency spectrum of CNVs detected in 15 inbred
Drosophila melanogaster lines by Emerson et al. (2008). The data are shown before and
after correcting for the ascertainment bias due to undetected mutations present in the
reference genome. The correction in this case is to divide each bin by 1-p. When the
reference genome is an outbred individual, corrections are more complicated. If the
“presence” allele is always represented when individuals are heterozygous for
duplications or deletions, we could assume that the only missed sequences would be
homozygous deletions in the reference individual or duplications present in either the
homozygous or heterozygous state in the reference individual. This means that the
correction would simply be to divide by 1-p2 in the case deletions and to divide by 1-(1p)2 in the case of duplications. However, given the almost unfathomable proclivities of
assembly software, we may never be able to confidently say that one allele or another
makes it into the reference consistently. In addition, in cases where multiple outbred
individuals were sequenced in order to construct the reference genome—as in humans—
there is no straightforward correction possible.