As expected, the majority (72%) of the WSSD intervals without assembly support for duplications (WGAC negative) were confirmed by FISH.
Our observation that the fragile regions in the human genome are correlated with segmental duplications suggests that negative selection is unlikely to be the sole source of observed variations in fragility, assuming the segmental duplications found in the human genome are not conserved in those other species in which these regions are in fact disrupted.
Immediately after duplication, the pressure of negative selection weakens and pairs of genes start evolving rapidly, possibly until both acquire important, but different, physiological roles.
In the RNase P CNR assay, four individuals, two with a deletion, one with duplication, and two CNV negative control individuals were tested using primer pairs designed to detect duplication and deletion in the same assay.
36, 48 If one assumes that all CMT1 patients with a negative PMP22 duplication on initial screening will go on to get panel testing as a second step, then we can evaluate the practicality of initial targeted testing of the PMP22 duplication versus including it as part of an initial multigene panel screen.
In the present case, the duplication has a strong, negative effect on male fertility that is a direct consequence of drive (Angelard et al. 2008; Atlan et al. 2003; Atlan et al. 2004) and should cause many other perturbations via overexpression of the six duplicated genes or rIST and Hosim1-SR activity.
Our hypothesis of a duplicability advantage for negative auto-regulators, however, principally applies to smaller scale duplications.
In one such study [ 1], it was shown that a subset of ovarian cancers share a marked tandem duplication phenotype with triple-negative breast cancers.
Indeed, the negative correlation between duplication span and sequence asymmetry in this study provides indirect evidence for the hypothesis that attenuated duplication spans create daughter copies that violate the assumption of sequence and functional redundancy with the ancestral locus, thereby initiating novel evolutionary trajectories for the derived loci.
Although in the primate lineage it would appear that the original episodes of positive selection following duplication were usually followed by negative selection.
