Genetic basis of susceptibility to teratogen induced birth defects

Authors

  • Bogdan J. Wlodarczyk,

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    • Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723.
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    • Bogdan J. Wlodarczyk is an assistant Professor at the Dell Pediatric Research Institute and holds a faculty position in the Department of Nutritional Sciences, The University of Texas at Austin. He is a reproductive toxicologist and uses animal models to study the mechanisms of birth defects.

  • Ana M. Palacios,

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    • Ana M. Palacios is a physician whose clinical activities and research have focused mainly on clinical genetics and neural tube defects. She has been involved in the creation and consolidation of two independent birth defect surveillance programs in Colombia and Nicaragua. Currently she is a graduate student in Dr. Richard Finnell's laboratory.

  • Claudia J. Chapa,

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    • Claudia J. Chapa is a physician currently involved in the Medical Genetics research team in Dr. Richard Finnell's laboratory. Her main research interest is in identifying genetic polymorphisms in patients with birth defects.

  • Huiping Zhu,

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    • Huiping Zhu is an assistant Professor at the Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin. Dr. Zhu has a doctoral degree in epidemiology, and has been working on birth defects etiology, especially gene-environment interactions.

  • Timothy M. George,

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    • Timothy M. George is the Chief of Pediatric Neurosurgery and Neurosciences at the Dell Children's Medical Center in Austin, Additionally; he is an Adjunct Professor of Cell and Molecular Biology at the University of Texas at Austin and serves as Director of the Pediatric Educational and Translational Research Institute. Dr George serves on Biomedical Engineering Advisory Board and the McComb Business School Health Care Initiative Advisory Board at the University of Texas at Austin. His research focuses on the molecular genetics of neural tube defects.

  • Richard H. Finnell

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    • Richard H. Finnell is a Professor in the Department of Nutritional Sciences and in the Department of Chemistry and Biochemistry at the University of Texas at Austin, and serves as the Director of Genomic Research at Dell Children's Medical Center. A pediatric geneticist, he has a distinguished career researching environmentally induced birth defects. Research in the Finnell Laboratory focuses on the interaction between specific genes and nutritional factors as they influence normal embryonic development and susceptibility to complex birth defects.


  • How to cite this article: Wlodarczyk B, Palacios A, Chapa C, Zhu H, George TM, Finnell RH. 2011. Genetic basis of susceptibility to teratogen induced birth defects. Am J Med Genet Part C Semin Med Genet 157:215–226.

Abstract

Birth defects remain the leading cause of infant death in US. The field of teratology has been focused on the causes and underlying mechanisms of birth defects for decades, yet our understanding of these critical issues remain unacceptably vague. Conclusions from years of animal and human studies made it clear that the vast majority of birth defects have multifactorial origins, with contributions from environmental and genetic factors. The environment comprises not only of the physical, biological, and chemical external environment surrounding the pregnant woman, but it also includes the internal environment of the woman's body that interact with the developing embryo in a complex fashion. The importance of maternal and embryonic genetic factors consisting of countless genetic variants/mutations that exist within every individual contribute to birth defect susceptibility is only now being more fully appreciated. This great complexity of the genome and its diversity within individuals and populations seems to be the principal reason why the same teratogenic exposure can induce severe malformation in one embryo, while fail to do so to other exposed embryos. As the interaction between genetic and environmental factors has long been recognized as the first “Principle of Teratology” by Wilson and Warkany [1965. Teratology: Principles and techniques. Chicago: University of Chicago Press], it is only recently that the appropriate investigative tools have been developed with which to fully investigate this fundamental principle. The introduction of high throughput technologies like whole genome sequencing or genome-wide association studies are promising to deliver an enormous amount of new data that will shed light on the genomic factors that contribute susceptibility to environmental teratogens. In this review, we attempt to summarize the epidemiological and experimental literature concerning birth defects whose phenotypic expression can be clearly related to the interactions between several select environmental factors and those genetic pathways in which they are most likely to have significant modifying effects. © 2011 Wiley-Liss, Inc.

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