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Genetics of Individuality

Periodic Reporting for period 1 - IndiGene (Genetics of Individuality)

Reporting period: 2019-02-01 to 2020-07-31

Individuality is both the defining feature of us and an important factor that affects our well-being. Genetic, environmental and random variation must all be understood if we hope to realize personalized medicine and fully understand biological systems across species. Our central aim is to investigate the sources of variation that result in differences between individuals.

This project makes use of the unique properties of medaka fish. Medaka can be fully inbred from the wild, are fertile and we have already sequenced of a panel of 111 inbred medaka lines originating from a single natural population. We will carry out in-depth profiling of these fish at multiple scales, ranging from molecular measurements to full organisms. We will analyse a number of traits in wild fish from the same source population, which will both increase our research potential and place our discoveries in the same context as human observational studies. A particular focus will be integrating this information across the cardiovascular systems, especially in comparison to human disease. We will host a “Research Hotel” that will provide and distribute the inbred medaka lines for other research projects that can be applied to this panel. This study will focus on the question of distinguishing between variation that occurs due to genetic, individual and environmental effects. This will lead to a more complete understanding of variation related to human disease and well-being.
Major achievements during this reporting period include the generation of further genetic resources from the Medake Inbred Kiyosu-Karlsruhe (MIKK) panel, significant progress on large scale phenotyping and the drafting of a flagship manuscript with a planned submission before the end of 2020. We have generated long read sequence data and built individual line specific genome reference assemblies for a subset of the MIKK panel and have generated a graph based MIKK panel ‘pan genome’ reference dataset. The RNA sequencing pilot sequencing and analysis has been completed allowing the optimised design of the environment (summer / winter) contrast for the first RNA sequencing project across the MIKK panel. The sequencing details have been defined and the samples are already in the sequencing pipeline at Sanger with data expected before the end of 2020. Phenotyping assays across the MIKK panel has been completed for three specific traits, heart rate, vertebrae numbers and behavioural traits, with F2 cross experiments having been designed and breeding lines setup up for vertebrae numbers and behavioural traits.
We have generated a graph based 'pan genome' reference datasets for the MIKK panel genomes. We will be making a MIKK panel specific graph genome reference available to the community before the end of the project.