September 22, 2019  |  

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

Authors: Lilue, Jingtao and Doran, Anthony G and Fiddes, Ian T and Abrudan, Monica and Armstrong, Joel and Bennett, Ruth and Chow, William and Collins, Joanna and Collins, Stephan and Czechanski, Anne and Danecek, Petr and Diekhans, Mark and Dolle, Dirk-Dominik and Dunn, Matt and Durbin, Richard and Earl, Dent and Ferguson-Smith, Anne and Flicek, Paul and Flint, Jonathan and Frankish, Adam and Fu, Beiyuan and Gerstein, Mark and Gilbert, James and Goodstadt, Leo and Harrow, Jennifer and Howe, Kerstin and Ibarra-Soria, Ximena and Kolmogorov, Mikhail and Lelliott, Chris J and Logan, Darren W and Loveland, Jane and Mathews, Clayton E and Mott, Richard and Muir, Paul and Nachtweide, Stefanie and Navarro, Fabio C P and Odom, Duncan T and Park, Naomi and Pelan, Sarah and Pham, Son K and Quail, Mike and Reinholdt, Laura and Romoth, Lars and Shirley, Lesley and Sisu, Cristina and Sjoberg-Herrera, Marcela and Stanke, Mario and Steward, Charles and Thomas, Mark and Threadgold, Glen and Thybert, David and Torrance, James and Wong, Kim and Wood, Jonathan and Yalcin, Binnaz and Yang, Fengtang and Adams, David J and Paten, Benedict and Keane, Thomas M

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.

Journal: Nature genetics
DOI: 10.1038/s41588-018-0223-8
Year: 2018

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