title: Harnessing genomics to identify environmental determinants of heritable disease.
abstract: Next-generation sequencing technologies can now be used to directly measure heritable de novo DNA sequence mutations in humans. However, these techniques have not been used to examine environmental factors that induce such mutations and their associated diseases. To address this issue, a working group on environmentally induced germline mutation analysis (ENIGMA) met in October 2011 to propose the necessary foundational studies, which include sequencing of parent-offspring trios from highly exposed human populations, and controlled dose-response experiments in animals. These studies will establish background levels of variability in germline mutation rates and identify environmental agents that influence these rates and heritable disease. Guidance for the types of exposures to examine come from rodent studies that have identified agents such as cancer chemotherapeutic drugs, ionizing radiation, cigarette smoke, and air pollution as germ-cell mutagens. Research is urgently needed to establish the health consequences of parental exposures on subsequent generations.
authors.affiliation: Health Canada, Canada. Electronic address: carole.yauk@hc-sc.gc.ca.
authors.forename: Carole Lyn
authors.initials: CL
authors.lastname: Yauk
authors.affiliation: Colorado State University, United States.
authors.forename: J
authors.initials: J
authors.lastname: Lucas Argueso
authors.affiliation: National Institute of Environmental Health Sciences, United States.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Auerbach
authors.affiliation: Université de Montréal, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Awadalla
authors.affiliation: National Institutes of Health, United States.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Davis
authors.affiliation: United States Environmental Protection Agency, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: DeMarini
authors.affiliation: Health Canada, Canada.
authors.forename: George R
authors.initials: GR
authors.lastname: Douglas
authors.affiliation: University of Leicester, United Kingdom.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Dubrova
authors.affiliation: United States Food and Drug Administration, United States.
authors.forename: Rosalie K
authors.initials: RK
authors.lastname: Elespuru
authors.affiliation: University of Michigan, United States.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Glover
authors.affiliation: McGill University, Canada.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Hales
authors.affiliation: Wellcome Trust Sanger Institute, United Kingdom.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.affiliation: New York University School of Medicine, United States.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Klein
authors.affiliation: Baylor College of Medicine, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Children's Hospital Colorado, United States.
authors.forename: David K
authors.initials: DK
authors.lastname: Manchester
authors.affiliation: Health Canada, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchetti
authors.affiliation: McGill University, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.affiliation: University of Oklahoma Health Sciences Center, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mulvihill
authors.affiliation: McGill University, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.affiliation: University of California Los Angeles, United States.
authors.forename: Wendie A
authors.initials: WA
authors.lastname: Robbins
authors.affiliation: Université de Montréal, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.affiliation: National Institute of Environmental Health Sciences, United States.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Shaughnessy
authors.affiliation: University of Regina, Canada.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Somers
authors.affiliation: National Heart Lung and Blood Institute, United States.
authors.forename: James G
authors.initials: JG
authors.lastname: Taylor
authors.affiliation: McGill University, Canada.
authors.forename: Jacquetta
authors.initials: J
authors.lastname: Trasler
authors.affiliation: Integrated Laboratory Systems, Inc, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Waters
authors.affiliation: University of Michigan, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wilson
authors.affiliation: National Institute of Environmental Health Sciences, United States.
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Witt
authors.affiliation: National Institute of Environmental Health Sciences, United States.
authors.forename: Jack B
authors.initials: JB
authors.lastname: Bishop
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity; D059647:Gene-Environment Interaction; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D023281:Genomics; D018095:Germ-Line Mutation; D006801:Humans; D011830:Radiation Effects; D062789:Tobacco Products / Q000009:adverse effects
chemical_list: D004785:Environmental Pollutants