Gene expression in teratogenic exposures: A new approach to understanding individual risk

- Many teratogen paradigms produce incomplete penetrance, with only some individuals affected.
- Comparisons between normal and exposed individuals cannot explain partial penetrance.
- We propose differences between exposed subjects as key factors in susceptibility.
- We illustrate this concept for two models for diabetes-induced neural tube defects.
- A focus on variability offers a new perspective to gene discovery in teratogenesis.

The phenomenon of partial or incomplete penetrance is common to many paradigms of exposure to teratogens, where only some of the exposed individuals exhibit developmental defects. We here argue that the most widely used experimental approaches in reproductive toxicology do not take partial penetrance into account, and are thus likely to miss differences between affected and unaffected individuals that contribute to susceptibility for teratogenesis. We propose that focus on the variation between exposed individuals could help to discover factors that may play a causative role for abnormal developmental processes that occur with incomplete penetrance.