&gt;&quot;Are you unaware that Sanger Sequencing exists, and the actual lesions can be read? Or that heterologous genes are being introduced with CRISPR methods? Neither of these common results can be explained by the spontaneous insertion of hundreds of nucleotides that happen to precisely match the sequence of the construct being inserted.&quot;<p>The first is just as consistent with the selection mechanism, because low levels of baseline mutants ARE reported (see the Schumann et al and Hendel et al papers I linked to in this thread for examples).<p>The second would indeed be difficult to explain with a selection mechanism, unfortunately I have not seen that actually published. Instead, the primers used can just as well be amplifying the template and&#x2F;or the sequence of the inserted cassette is not shown (eg Figure 2D and S1 here: <a href="http:&#x2F;&#x2F;www.sciencemag.org&#x2F;content&#x2F;348&#x2F;6233&#x2F;442" rel="nofollow">http:&#x2F;&#x2F;www.sciencemag.org&#x2F;content&#x2F;348&#x2F;6233&#x2F;442</a> )<p>If you have a reference to a specific paper I would appreciate it.