The Impact of Environmental Factors on Monogenic Mendelian Diseases.

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Environmental factors and gene-environment interactions modify the variable expressivity, progression, severity, and onset of some classic (monogenic) Mendelian-inherited genetic diseases. Cystic Fibrosis, Huntington Disease, Parkinson's Disease, and Sickle Cell Disease are examples of well-known Mendelian disorders that are influenced by exogenous exposures. Environmental factors may act by direct or indirect mechanisms to modify disease severity, timing, and presentation, including through epigenomic influences, protein misfolding, miRNA alterations, transporter activity, and mitochondrial effects. Since pathological features of early-onset Mendelian diseases can mimic later onset complex diseases, we propose that studies of environmental exposure vulnerabilities using monogenic model systems of rare Mendelian diseases have high potential to provide insight into complex disease phenotypes arising from multi-genetic/multi-toxicant interactions. Mendelian disorders can be modeled by homologous mutations in animal model systems with strong recapitulation of human disease etiology and natural history, providing an important advantage for study of these diseases. Monogenic high penetrant mutations are ideal for toxicant challenge studies with a wide variety of environmental stressors, since background genetic variability may be less able to alter the relatively strong phenotype driving disease-causing mutations. These models promote mechanistic understandings of gene-environment interactions and biological pathways relevant to both Mendelian and related sporadic complex disease outcomes by creating a sensitized background for relevant environmental risk factors. Additionally, rare disease communities are motivated research participants, creating the potential of strong research allies among rare Mendelian disease advocacy groups and disease registries and providing a variety of translational opportunities that are under-utilized in genetic or environmental health science.





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Tukker, Anke M, Charmaine D Royal, Aaron B Bowman and Kimberly A McAllister (2021). The Impact of Environmental Factors on Monogenic Mendelian Diseases. Toxicological sciences : an official journal of the Society of Toxicology. 10.1093/toxsci/kfab022 Retrieved from

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Charmaine DM Royal

Robert O. Keohane Professor of African & African American Studies

Charmaine Royal is the Robert O. Keohane Professor of African & African American Studies, Biology, Global Health, and Family Medicine & Community Health at Duke University. She directs the Duke Center on Genomics, Race, Identity, Difference and the Duke Center for Truth, Racial Healing & Transformation.

Dr. Royal’s research, scholarship, and teaching focus on ethical, social, scientific, and clinical implications of human genetics and genomics, with an emphasis on issues at the intersection of genetics and race. Her interests and primary areas of work include genetics and genomics in African and African Diaspora populations; sickle cell disease and trait; public and professional perspectives and practices regarding race, ethnicity, and ancestry; genetic ancestry inference; and genotype-environment interplay. A fundamental aim of her work is to dismantle ideologies and systems of racial hierarchy in science, healthcare, and society. She serves on numerous national and international advisory boards and committees for government agencies, professional organizations, research initiatives, not-for-profit entities, and corporations.

Dr. Royal obtained a bachelor’s degree in microbiology, master’s degree in genetic counseling, and doctorate in human genetics from Howard University. She completed postgraduate training in ethical, legal, and social implications (ELSI) research and bioethics at the National Human Genome Research Institute of the National Institutes of Health, and in epidemiology and behavioral medicine at Howard University Cancer Center.

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