How do transgenic transformations cause off-target phenotypes?
I read that transgene insertions can cause off-target mutations that result in a phenotype being overly ascribed to the transgene, e.g. the increase of lifespan being ascribed to Sir2 overexpression (Burnett et al, 2011, https://www.ncbi.nlm.nih.gov/pubmed/21938067). In that particular study, they outcrossed the transgenic strain several times with wild-type to remove these off-target effects, a mutation in Dyf2 being named in particular.I have a poor background in genetics, so I don't really understand how transgene insertions can cause off-target mutations, nor how outcrossing can isolate the intended mutation.
DNA is regulated in a three dimensional way sometimes. Take your thumbs, place them side by side. The nails match up on top of each other. Pretend your thumb is longer now using your index finger. The nails no longer match up. Let's say the nail is a promoter targeting the other nail. Now that they are no longer aligned the protein cannot reach both nails and thus down regulation would occur.
