Evidence for germline non-genetic inheritance of human phenotypes and diseases

Abstract

It is becoming increasingly apparent that certain phenotypes are inherited across generations independent of the information contained in the DNA sequence, by factors in germ cells that remain largely uncharacterized. As evidence for germline non-genetic inheritance of phenotypes and diseases continues to grow in model organisms, there are fewer reports of this phenomenon in humans, due to a variety of complications in evaluating this mechanism of inheritance in humans. This review summarizes the evidence for germline-based non-genetic inheritance in humans, as well as the significant challenges and important caveats that must be considered when evaluating this process in human populations. Most reports of this process evaluate the association of a lifetime exposure in ancestors with changes in DNA methylation or small RNA expression in germ cells, as well as the association between ancestral experiences and the inheritance of a phenotype in descendants, down to great-grandchildren in some cases. Collectively, these studies provide evidence that phenotypes can be inherited in a DNA-independent manner; the extent to which this process contributes to disease development, as well as the cellular and molecular regulation of this process, remain largely undefined.

The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review

“…There is increasing evidence that epigenetic information can reach across generations independent of genetic transmission [ 151 ]. Recent studies have described some mechanisms by which non-genetic information is relayed independently of the nucleotide sequence.…”

On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics

“…Possibly the strongest evidence that our ancestors were not routinely deprived of calories, though, comes from the field of epigenetics. Many of the studies in this field focus on natural experiments, where humans were starved due to external factors such as war or famine [19]. Children and grandchildren of those underfed individuals show a strong predisposition toward obesity and heart disease, as well as diabetes and other metabolic problems.…”

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

“…In recent years, the central dogma has been updated (Morange, 2009;Shapiro, 2009;Koonin, 2012;Koonin, 2015;Tan & Anderson, 2020), but basically no change has been made in the role of DNA as the ultimate carrier of all heritable information passed on to new generations. In recent years, however, there has been increasing interest in transgenerational epigenetic inheritance in the scientific research community, increasing the focus on heritable information that is not transmitted through the genome, but through the epigenome (Lange & Schneider, 2010;Prokopuk et al, 2015;Blake & Watson, 2016;Xavier et al, 2019;Liberman et al, 2019;Duempelmann et al, 2020;Senaldi & Smith-Raska, 2020). On top of that, the GWAS studies, mentioned before, are part of a central problem nowadays in biology: the missing heritability problem (Manolio et al, 2009).…”