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WIREs Dev Biol
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Gene–environment interactions in development and disease

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Developmental geneticists continue to make substantial jumps in our understanding of the genetic pathways that regulate development. This understanding stems predominantly from analyses of genetically tractable model organisms developing in laboratory environments. This environment is vastly different from that in which human development occurs. As such, most causes of developmental defects in humans are thought to involve multifactorial gene–gene and gene–environment interactions. In this review, we discuss how gene–environment interactions with environmental teratogens may predispose embryos to structural malformations. We elaborate on the growing number of gene–ethanol interactions that might underlie susceptibility to fetal alcohol spectrum disorders. WIREs Dev Biol 2017, 6:e247. doi: 10.1002/wdev.247 This article is categorized under: Early Embryonic Development > Development to the Basic Body Plan Birth Defects > Associated with Preimplantation and Gastrulation Birth Defects > Craniofacial and Nervous System Anomalies
Timing of teratogen exposure can dictate disrupted organ systems. The timing of development of several organ systems discussed in this review is listed. The long development of the central nervous system (CNS) makes it particularly susceptible to teratogenic insult.
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Complexity of gene–environment interactions. Multiple gene–environment interactions are involved in even the simplest model of ethanol teratogenesis. Prenatal alcohol exposure is required for the development of fetal alcohol spectrum disorders (FASD), but is, itself, regulating by gene–environment interactions that mediate both consumption patterns and ethanol metabolism. Prenatal development, then, can be thought of as a set of complex, hierarchical, and often interrelated gene–environment interactions.
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Facial features characteristic of fetal alcohol syndrome.
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Environmental influences on development. A developing embryo or fetus (center) can be exposed to numerous environmental factors. These factors can interact with the genetic susceptibility of the developing embryo or fetus to alter the outcome of development.
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Birth Defects > Associated with Preimplantation and Gastrulation
Birth Defects > Craniofacial and Nervous System Anomalies
Early Embryonic Development > Development to the Basic Body Plan