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Genetics of Individuality

Periodic Reporting for period 2 - IndiGene (Genetics of Individuality)

Reporting period: 2020-08-01 to 2022-01-31

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 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 publication of two flagship manuscripts describing genetic and phenotypic variability across the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. Both manuscripts have been published as companion papers in Genome Biology and represent a large body of work characterising the MIKK panel in detail.
Another manuscript describing the application of base editing to immediately target individual nucleotides in complex genomes is at a comparable state.

Due to the global pandemic we have had certain difficulties in generating further genetic sequencing data with our sequencing partners having capacity issues due to sequencing of SARS-CoV2 samples and simply a reduced capacity and social distancing requirements within the sequencing labs. However, we have now been able to get some further sequencing work fully planned and into the sequencing queues with the expectation of data generation later this year, for the large RNA sequencing experiment and further long read sequencing of the entire MIKK panel.
Further phenotyping of the MIKK panel and F2 cross designs have also been impacted by the global pandemic however full panel wide phenotypes, additional phenotypic measurement analysis and F2 cross generation has been completed for three specific traits, heart rate, vertebrae numbers and behavioural traits. F2 cross populations have been set up and are productive with planned large scale phenotyping and sequencing to happen during the next reporting period.
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.