Reanalyzing variable directionality of gene expression in transgenerational epigenetic inheritance

TL;DR

This paper reexamines evidence for transgenerational epigenetic inheritance in mice, clarifying statistical and conceptual issues in previous studies that questioned the phenomenon.

Contribution

It demonstrates that previous criticisms were based on incorrect statistics and misconceptions about gene expression as a phenotype, supporting the existence of transgenerational inheritance.

Findings

Previous criticisms were based on incorrect statistical analysis.

Gene expression changes are valid phenotypic indicators.

The study supports the occurrence of transgenerational epigenetic inheritance.

Abstract

A previous report claimed no evidence of transgenerational epigenetic inheritance in a mouse model of in utero environmental exposure, based on the observation that gene expression changes observed in the germ cells of G1 and G2 male fetus were not in the same direction. A subsequent data reanalysis however showed a statistically significant overlap between G1 and G2 genes irrespective of direction, leading to the suggestion that, as phenotypic variability in epigenetic transmission has been observed in several other examples also, the above report provided evidence in favor of, not against, transgenerational inheritance. This criticism has recently been questioned. Here, it is shown that the questions raised are based not only on incorrect statistical calculations but also on wrong premise that gene expression changes do not constitute a phenotype.