Scientific Publications by FDA Staff

Mutat Res 2013 Jan-Mar;752(1):6-9

Harnessing genomics to identify environmental determinants of heritable disease.

Yauk CL, Lucas Argueso J, Auerbach SS, Awadalla P, Davis SR, Demarini DM, Douglas GR, Dubrova YE, Elespuru RK, Glover TW, Hales BF, Hurles ME, Klein CB, Lupski JR, Manchester DK, Marchetti F, Montpetit A, Mulvihill JJ, Robaire B, Robbins WA, Rouleau GA, Shaughnessy DT, Somers CM, Taylor JG 6th, Trasler J, Waters MD, Wilson TE, Witt KL, Bishop JB

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.