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Summary
Full paper available at https://www.biorxiv.org/content/10.1101/2021.05.17.444412v2.full
Unraveling the relationship between genetic variation and phenotypic traits remains a fundamental challenge in biology. Mapping variants underlying complex traits while controlling for confounding environmental factors is often problematic. To address this, we have established a vertebrate genetic resource specifically to allow for robust genotype-to-phenotype investigations. The teleost medaka (Oryzias latipes) is an established genetic model system with a long history of genetic research and a high tolerance to inbreeding from the wild. Here we present the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel: the first near-isogenic panel of 80 inbred lines in a vertebrate model derived from a wild founder population. Inbred lines provide fixed genomes that are a prerequisite for the replication of studies, studies which vary both the genetics and environment in a controlled manner and functional testing. The MIKK panel will therefore enable phenotype-to-genotype association studies of complex genetic traits while allowing for careful control of interacting factors, with numerous applications in genetic research, human health, and drug development and fundamental biology. Here we present a detailed characterisation of the genetic variation across the MIKK panel, which provides a rich and unique genetic resource to the community by enabling large-scale experiments for mapping complex traits.
About tissue
For whole genome sequencing, medaka organs were dissected from 6-month-old male adults. Fish were sacrificed by hypothermic shock. The brain was dissected and shock frozen in liquid nitrogen. For RNAseq analysis 12 month old adults that were kept at either 14 light:10 dark (summer condition) or 10 light:14 dark (winter condition) light cycles respectively were sacrificed by hypothermic shock and the organs after dissection were shock frozen in liquid nitrogen.
Acknowledgment
The authors acknowledge Thomas Seitz, and Irina Oks and Marzena Majewski for supporting the fish husbandry, and Alicia Günthel, Rachel Müller and Beate Wittbrodt for laboratory assistance. F.L. dedicates this paper to Sabine and Rolf Loosli-Walther. The work was funded by the Helmholtz funding programme BIFTM to F. Loosli, N. Wolf, N. Kusminski, C. Herder and N. Aadepu. E. Birney, T. Fitzgerald, A. Leger, C. Barton, J. Monahan and I. Brettell were funded by the EMBL European Bioinformatics Institute (EMBL-EBI). This work was supported by Heidelberg University Core Funding to T. Tavhelidse, T. Thumberger and J. Wittbrodt. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 810172), from the NIH UH-3338-03 (JW), the German Ministry for Research (BMBF: HIGH-life 05K19VH1, Code-Vita 05K16VH1, JW) and the German Center for Heart Diseases DZHK (JW, JG).