unintended "side-effects" of gene therapy

Mike Lieber (U28550@UICVM.BITNET)
Tue, 7 Mar 1995 16:36:07 CST

When I asked Lawrence Leichtman about unintended effects, I had in mind
systemic effects of replacing one gene with another. Two things come to
mind--polygenic effects and pleiotropy, both common in genetic organization.
To the extent that a phenotypic outcome is the result of a polygene, a
sequence of genes whose proteins trigger a sequence of chemical reactions,
there is a possibility that an allele that works quite well in one
combination of alleles would not work well with a different combination of
alleles in the same sequence. A variant of this is pleiotropy, the same
gene being part of two or more different polygenes (and thus two different
chemical pathways to different phenotypic outcomes). A particular allele
may work well in one sequence but not in another. In both these sorts of
cases, the phenotypic outcomes may be quite different from what the
researcher expected, and, depending on where in the sequence the replacing
gene is located, the outcome may be more far reaching than the researcher
anticipated. The earlier in the sequence the allele occurs, the greater the
systemic effect it has. I wonder if these sorts of ussies are beingf discussed
among geneticists working on the project or thinking about the project.

Mike Lieber