Final Report Summary - SIGHT (Systems Genetics of Heritable variaTions)
We have established a novel concept to detect and characterize genetic effects that had so far not been considered. The concept, which we named "Particle Genetics", is based on the fact that mutations can generate non-deterministic changes of molecular and cellular regulations: even if all cells carry the mutation, the biological disturbance may occur in only some of the cells, in a probabilistic manner. During the project, we experimentally discovered and characterized several examples of such mutations, and we provided evidence that such probabilistic effects are abundant in living systems. We built and validated a statistical method and software to identify such mutations of the genome. The method is radically different from the genome-scan methods commonly used in genetics. It exploits phenotypic traits acquired on populations of individual cells extracted from genotypically-distinct donor individuals.
We also provided a better understanding of the natural quantitative variation of chromatin epigenetic marks, by showing that it has a dual nature (both genetic and non-genetic), and that it displays a complex pattern of co-variation between marks and between marks and transcriptional levels.
We also provided a better understanding of the natural quantitative variation of chromatin epigenetic marks, by showing that it has a dual nature (both genetic and non-genetic), and that it displays a complex pattern of co-variation between marks and between marks and transcriptional levels.