Constitutional Epi/Genetic Conditions: Genetic, Epigenetic, and Environmental Factors.
There are more than 4,000 phenotypes for which the molecular basis is at least partly known. Though defects in primary DNA structure constitute a major cause of these disorders, epigenetic disruption is emerging as an important alternative mechanism in the etiology of a broad range of congenital and developmental conditions. These include epigenetic defects caused by either localized (in cis) genetic alterations or more distant (in trans) genetic events but can also include environmental effects. Emerging evidence suggests interplay between genetic and environmental factors in the epigenetic etiology of several constitutional "epi/genetic" conditions. This review summarizes our broadening understanding of how epigenetics contributes to pediatric disease by exploring different classes of epigenomic disorders. It further challenges the simplistic dogma of "DNA encodes RNA encodes protein" to best understand the spectrum of factors that can influence genetic traits in a pediatric population.
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada.
Laila C
LC
Schenkel
Children's Health Research Institute, London, Ontario, Canada; Department of Biochemistry, Western University, London, Ontario, Canada; Department of Pediatrics, Western University, London, Ontario, Canada; London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada.
David
D
Rodenhiser
Children's Health Research Institute, London, Ontario, Canada; Department of Pediatrics, Western University, London, Ontario, Canada; London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
Victoria
V
Siu
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Elizabeth
E
McCready
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada; Department of Biochemistry, Western University, London, Ontario, Canada; Department of Pediatrics, Western University, London, Ontario, Canada; London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada.
Peter
P
Ainsworth
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada.
Bekim
B
Sadikovic
DNA methylation; environmental exposures; epigenetics; genetic syndromes; imprinting; pediatric diseases