We pursued this analysis further given strong evidence that certain rare transmitted CNVs carry ASD risk, as well as reports of particularly significant effects for maternal transmission of rare CNVs to male probands (Zhao et al., 2007). Consequently, we investigated whether mothers were more likely than fathers to transmit a rare CNV to an affected offspring. We also asked whether there were a greater number of maternally transmitted CNVs in probands versus their unaffected siblings. Neither analysis showed a significant result after correction for multiple comparisons despite considering combinations of the following variables: deletions, duplications, size, exonic, brain-expressed, and ASD-related. In addition, based on the possibility that risk might be confined to only the rarest transmitted events, presumably under the strongest purifying selection, we evaluated “singleton” CNVs, i.e. those observed in only one parent and transmitted to only one proband or sibling. In this case, we found a modest, non-significant excess of maternally transmitted CNVs in probands: 344 maternal autosomal singletons are transmitted to probands vs. 303 transmissions to siblings (OR= 1.14; p=0.059 one-sided; p=0.12 two-sided). For fathers, there was no similar trend (OR= 1.03; p=0.37 one-sided).
