1. Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci
- Author
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Dent Earl, Monica Abrudan, Benedict Paten, Adam Frankish, Lesley Shirley, Cristina Sisu, Ian T. Fiddes, Mark Gerstein, James G. R. Gilbert, Mark G. Thomas, Anne Czechanski, Duncan T. Odom, William Chow, Stephan C. Collins, Clayton E. Mathews, Mark Diekhans, Ruth Bennett, Jane E. Loveland, David J. Adams, Jingtao Lilue, Beiyuan Fu, Dirk-Dominic Dolle, Fengtang Yang, Laura G. Reinholdt, Glen Threadgold, Anne C. Ferguson-Smith, Jonathan Wood, Kim Wong, Leo Goodstadt, Paul R. Muir, Thomas M. Keane, Phan Sk, Jonathan Flint, Naomi R Park, Richard Mott, Joel Armstrong, Thybert D, Jen Harrow, Petr Danecek, Marcela K. Sjoberg-Herrera, Sarah Pelan, Anthony G. Doran, Kerstin Howe, Charles A. Steward, Mario Stanke, Binnaz Yalcin, Joanna Collins, Lelliott C, Matthew Dunn, Fabio C. P. Navarro, Michael A. Quail, Paul Flicek, James Torrance, Richard Durbin, Köenig S, Lars Romoth, and Mikhail Kolmogorov
- Subjects
Genetics ,0303 health sciences ,Strain (biology) ,Haplotype ,Genomics ,Retrotransposon ,Biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Genome Reference Consortium ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology ,Reference genome - Abstract
The most commonly employed mammalian model organism is the laboratory mouse. A wide variety of genetically diverse inbred mouse strains, representing distinct physiological states, disease susceptibilities, and biological mechanisms have been developed over the last century. We report full length draft de novo genome assemblies for 16 of the most widely used inbred strains and reveal for the first time extensive strain-specific haplotype variation. We identify and characterise 2,567 regions on the current Genome Reference Consortium mouse reference genome exhibiting the greatest sequence diversity between strains. These regions are enriched for genes involved in 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. Several immune related loci, some in previously identified QTLs for disease response have novel haplotypes not present in the reference that may explain the phenotype. We used these genomes to improve the mouse reference genome resulting in the completion of 10 new gene structures, and 62 new coding loci were added to the reference genome annotation. Notably this high quality collection of genomes revealed a previously unannotated gene (Efcab3-like) encoding 5,874 amino acids, one of the largest known in the rodent lineage. Interestingly, Efcab3-like−/− mice exhibit severe size anomalies in four regions of the brain suggesting a mechanism of Efcab3-like regulating brain development.
- Published
- 2018