4.5 Article

Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel

Journal

GENOME BIOLOGY
Volume 23, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13059-022-02602-4

Keywords

Inbred panel; Medaka; Genetics; Methylation; Structural variation; Graph genome; Long read sequencing; Pan genome; Nanopore

Funding

  1. Heidelberg University
  2. European Research Council (ERC) under the European Union [810172]
  3. NIH [UH3338-03]
  4. German Ministry for Research [BMBF: HIGH-life 05K19VH1, V ita 05K16VH1]
  5. German Center for Heart Diseases DZHK
  6. Helmholtz funding programme BIFTM
  7. EMBL European Bioinformatics Institute (EMBL-EBI)
  8. European Research Council (ERC) [810172] Funding Source: European Research Council (ERC)

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In this study, the researchers used long read data from Oxford Nanopore Technologies to analyze the genomes of medaka, creating a specific pan-genome reference dataset for the Medaka Inbred Kiyosu-Karlsruhe panel. This dataset allows for the investigation of novel variation types that would be difficult to detect using standard approaches.
Background The teleost medaka (Oryzias latipes) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains. Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals. Results We exploit this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We use Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allows us to identify a large variety of high-quality structural variants, and we present results and methods using a pan-genome graph representation of 12 individual medaka lines. This graph-based reference MIKK panel genome reveals novel differences between the MIKK panel lines and standard linear reference genomes. We find additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We are also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigate line-specific CpG methylation and performed differential DNA methylation analysis across these 12 lines. Conclusions We present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel-specific pan genome reference dataset allowing for investigation of novel variation types that would be elusive using standard approaches.

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