Quantitative epigenetics through epigenomic perturbation of isogenic lines

Area of Science:

• Genetics
• Epigenetics
• Quantitative genetics

Background:

• Interindividual differences in chromatin states (epialleles) can influence gene expression and contribute to heritable phenotypic variation independently of DNA sequence.
• Epialleles can exhibit transgenerational instability, introducing a dynamic element to inheritance beyond classical Mendelian genetics.

Purpose of the Study:

• To develop a general experimental approach for studying the induction and transgenerational behavior of epialleles.
• To incorporate non-Mendelian epigenetic inheritance into quantitative genetic models.
• To model the impact of epiallelic instability on phenotypic variation across generations.

Main Methods:

• Crosses of epigenomically perturbed isogenic lines in mammalian and plant species.
• Theoretical description and modeling of crosses, considering epiallelic instability, recombination, parent-of-origin effects, and transgressive segregation.
• Analysis of Arabidopsis epigenetic recombinant inbred lines to estimate quantitative trait loci related to plant height.

Main Results:

• The proposed approach integrates epigenetic inheritance with classical quantitative genetics, reducing to the latter in the case of stable epialleles.
• Modeling reveals the joint impact of epiallelic instability and other factors on phenotypic variation.
• Estimates of quantitative trait loci for plant height were explored in Arabidopsis, linked to DNA methylation manipulation.

Conclusions:

• The study provides a framework for integrating epigenetic inheritance into quantitative genetic models.
• Understanding epiallelic instability is crucial for explaining heritable phenotypic variation.
• This work highlights the continuity between genetic and epigenetic inheritance.