Inbred laboratory mouse strains descend from a small pool of founder animals, so any two strains differ at millions of sites and carry long stretches of distinct ancestral haplotype. The Mouse Genomes Project built de novo assemblies for 16 of them, 12 classical laboratory strains and 4 derived from wild mice, covering most of the genetic diversity in common laboratory use. Seven of the eight Collaborative Cross and Diversity Outbred founder strains are included; the eighth, C57BL/6J, is the reference assembly itself.
This track shows a whole-genome multiple alignment of those 16 strain assemblies to the mouse reference, with the rat genome included as an outgroup. It was built with Progressive Cactus from the assemblies themselves rather than by mapping short reads, so insertions and deletions in a strain appear directly in the alignment. Large rearrangements are a different matter: the strain scaffolds were joined into chromosomes using the reference as a guide, and adjacencies that disagreed with it were mostly discarded, so this is not a good source for translocations or inversions.
Note that the assembly included here is C57BL/6NJ, a substrain of the C57BL/6J animal the mouse reference was built from, so that row is nearly identical to the reference along most of the genome.
The alignment is symmetric, so it can also be viewed with any of the 16 strains as the reference instead of C57BL/6J. To do that, load the Mouse strain assemblies hub, which is on our public hub list, and pick a strain assembly from its gateway page.
Each aligned assembly is shown on its own row, labeled with the strain name. The track configuration page lets you choose which assemblies to display. The strains are listed there in three groups, wild-derived, classical laboratory, and rat, each with a pair of buttons that turn the whole group on or off at once.
To see the aligned bases at a given position, zoom in to 30,000 bases or fewer and click the alignment.
The Display chains between alignments configuration option enables display of gaps between alignment blocks, in a manner similar to the Chain track display. Missing sequence in any assembly is highlighted by regions of yellow when zoomed out and by Ns at base level. The conventions are:
Discontinuities in the genomic context (chromosome, scaffold or region) of the aligned DNA are shown as follows:
When zoomed in to base level, the track shows the base composition of each alignment. The numbers and symbols on the Gaps line indicate the lengths of gaps in the reference sequence at those alignment positions, relative to the longest non-reference sequence. If there is sufficient space in the display, the size of the gap is shown. If the space is insufficient and the gap size is a multiple of 3, a "*" is displayed; other gap sizes are indicated by "+".
Codon translation is available at base level when the displayed region is annotated as coding. To turn it on, pick a species in the Codon Translation section of the configuration page and then choose one of these modes:
The 16 strain assemblies were produced by the Mouse Genomes Project at the Wellcome Sanger Institute from Illumina paired-end reads at 40x to 70x coverage, mate-pair libraries at 3, 6 and 10 kb, and fosmid and BAC-end sequences. CAST/EiJ, PWK/PhJ and SPRET/EiJ were scaffolded further with Dovetail Genomics Chicago libraries through HiRise. Scaffolds were then joined into chromosome-scale sequences with Ragout v2.0, using the C57BL/6J GRCm38 sequence as the single reference and minimizing the number of structural differences from it. On average 10% of synteny block adjacencies in the assemblies were absent from the reference; Ragout kept the 38% of those it judged to be real rearrangements and removed the remainder as misassemblies. The GenBank version of each assembly was used here. A Progressive Cactus alignment was then generated from those 16 assemblies together with the mouse reference (mm10) and the rat reference (rn6), giving 18 genomes in total. Because the laboratory strains are so closely related, the Cactus guide tree was binarized as accurately as possible, but incomplete lineage sorting is common among these strains, and the guide tree may not be correct in every region. This has little effect on alignment quality except where insertions and deletions themselves fall under incomplete lineage sorting. The guide tree is shown on the track configuration page. See the references below for details of both the assemblies and the alignment method.
The alignment is served directly from the files behind the mouse strains assembly hub on our download server, at https://hgdownload.soe.ucsc.edu/hubs/mouseStrains/mm10/maf/. No reprocessing was done for this track; only the track configuration differs from the hub. The full alignment is also available in HAL format as mouseStrains_1509.hal, and the bigMaf files displayed here were generated from it.
The steps taken to add this track are recorded in doc/mm10/mouseStrainsCactus.txt, and its track configuration is in trackDb/mouse/mm10/mouseStrainsCactus.ra.
The alignment can be explored interactively with the Table Browser, which returns one MAF block per row. From scripts, the data can be accessed through our API, using the track name mouseStrainsCactus.
For automated download and analysis, the alignment is stored in bigMaf format and can be downloaded from our download server. The files are called mm10.bigMaf.bb (the alignment, roughly 9 GB), mm10.bigMafSummary.bb (the zoomed-out summary) and mm10.bigMafFrames.bb (the coding frames used for codon translation). Individual regions or the whole alignment can be converted to MAF with our tool bigMafToMaf, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool reads the file over the network, so a single region can be pulled out without downloading the whole alignment:
bigMafToMaf https://hgdownload.soe.ucsc.edu/hubs/mouseStrains/mm10/maf/mm10.bigMaf.bb \
region.maf -chrom=chr1 -start=3000000 -end=3100000
The 16 strain assemblies themselves can be downloaded from the Mouse Genomes Project archive at EMBL-EBI.
Alignment generation: Joel Armstrong, Ian Fiddes and Benedict Paten, UC Santa Cruz Genomics Institute. Genome assemblies: Thomas Keane and the Mouse Genomes Project, Wellcome Sanger Institute.
Hickey G, Paten B, Earl D, Zerbino D, Haussler D. HAL: a hierarchical format for storing and analyzing multiple genome alignments. Bioinformatics. 2013 May 15;29(10):1341-2. PMID: 23505295; PMC: PMC3654707
Lilue J, Doran AG, Fiddes IT, Abrudan M, Armstrong J, Bennett R, Chow W, Collins J, Collins S, Czechanski A et al. Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci. Nat Genet. 2018 Nov;50(11):1574-1583. PMID: 30275530; PMC: PMC6205630
Nguyen N, Hickey G, Raney BJ, Armstrong J, Clawson H, Zweig A, Karolchik D, Kent WJ, Haussler D, Paten B. Comparative assembly hubs: web-accessible browsers for comparative genomics. Bioinformatics. 2014 Dec 1;30(23):3293-301. PMID: 25138168; PMC: PMC4296145
Paten B, Earl D, Nguyen N, Diekhans M, Zerbino D, Haussler D. Cactus: Algorithms for genome multiple sequence alignment. Genome Res. 2011 Sep;21(9):1512-28. PMID: 21665927; PMC: PMC3166836