Figure 1

Potential genetic consequences of integration of transgenic cassettes into chromatin. An expression cassette (orange box) in a viral or nonviral vector (represented by purple inverted arrowheads, which indicate either inverted or direct terminal repeats) can integrate into four classes of chromatin. (1) Integration into heterochromatin will most likely result in the suppression of expression of the transgene and essentially no genetic consequences for the host. (2) Integration into intergenic regions of euchromatin is the most desirable outcome; the transgenic cassette is expressed, leading to a gain of function (GOF) in the host cell. (3) Integration into a transcriptional regulatory region can have several outcomes including expression (GOF) of the transgenic cassette, potentially modified by neighboring enhancer and silencer elements in the region. Regulatory elements in the transgenic cassette may either enhance expression of the neighboring gene (GOF for gene X) or, in rare cases, block expression of an active gene. (4) Integration of the vector into a transcriptional unit may allow expression of the transgene but block expression of the host gene leading to a phenotypic loss of function (LOF). Integration within some genes can also lead to a dominant gain of function (DGF) or production of a dominant-negative form (DNF) of the original gene X. A further discussion of effects of insertional mutagenesis can be found in the reports by Carlson and Largaespada [61] and Collier and Largaespada [154].