An Epigenetic Twist on the Missing Heritability of Complex Traits

RESEARCH HIGHLIGHTS

Nature Reviews Genetics | AOP, published online 18 February 2014; doi:10.1038/nrg3898

EPIGENETICS investigators then set out to elimi- nate the possibility that the causal An epigenetic twist on the missing variants underlying the QTLs were transposable element insertions in heritability of complex traits the parental line that shows reduced DNA methylation by re-sequencing P. Morgan/NPG Epigenetic variation has been sug- recombinant inbred A. thaliana lines a large number of epiRILs. Although gested as an explanation for the (epiRILs) from two essentially four shared transposable element missing heritability in complex traits. isogenic parents that had highly insertions were found in several A study now reports that experimen- divergent DNA methylomes. QTLs of the two traits, further work tally induced differentially methyl- Previous work showed that the showed that they were not causal. ated regions (DMRs) in Arabidopsis epiRILs segregate hundreds of The epiRIL QTLs are therefore most thaliana are stably inherited and act stable parental DMRs throughout likely the result of the heritable, as epigenetic quantitative trait loci the genome. Using these DMRs as induced loss of DNA methylation in (QTLsepi) independently of DNA physical markers, the authors carried the QTL intervals. sequence changes. out classical linkage mapping in the About 30% of the induced herit- To contribute to complex-trait epiRILs and identified various QTLs able DMRs that were identified in heritability independently of that underlie two highly heritable the epiRILs overlap with naturally DNA sequence variation, at least complex traits — primary root length occurring DMRs. The authors some epigenetic stability during and flowering time. The combined propose that these DMRs could also gametogenesis is necessary; that is, additive effects of these QTLs act as QTLsepi in natural populations epigenetic states must be transmitted accounted for ~60% and ~90% of the and thus constitute a measurable to the next generation intact. Cortijo heritability of primary root length component of the missing heritability and colleagues aimed to determine and flowering time, respectively. of complex traits. Linda Koch whether this stability is conferred by Linkage mapping results pin-

sequence-independent chromatin pointed the origin of the causal ORIGINAL RESEARCH PAPER Cortijo, S. et al. inheritance or by cis- or trans-acting variants that underlie heritability to Mapping the epigenetic basis of complex traits. DNA-based factors. The authors the parental generation as opposed Science http://dx.doi.org/10.1126/science.1248127 (2014) generated a population of epigenetic to later inbred generations. The

NATURE REVIEWS | GENETICS VOLUME 15 | APRIL 2014