Arising from I. F. King et al. Nature 501, 58–62 (2013); doi:10.1038/nature12504
In an important recent paper, King et al.1 reported that inhibition of TOP1 and other topoisomerases reduces the expression of extremely long genes. They also showed that the list of large genes affected by TOP1 inhibition is enriched with candidate genes for autism spectrum disorders (ASD); however, the list of candidate genes that was used contains many genes with limited evidence for association with ASD2. Here we demonstrate that the size of the genes among ASD candidate genes is biased towards extremely large genes only for genes identified to be disrupted by copy number variations (CNVs). Thus, our analysis suggests that the association between large genes and ASD is mainly driven by the method that implicated the genes in ASD. There is a Reply to this Brief Communication Arising by Zylka, M. J. et al. Nature 512, http://dx.doi.org/10.1038/nature13584 (2014).
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