Sequencing and characterization of the FVB/NJ mouse genome

Abstract

Background: The FVB/NJ mouse strain has its origins in a colony of outbred Swiss mice established in 1935 at the National Institutes of Health. Mice derived from this source were selectively bred for sensitivity to histamine diphosphate and the B strain of Friend leukemia virus. This led to the establishment of the FVB/N inbred strain, which was subsequently imported to the Jackson Laboratory and designated FVB/NJ. The FVB/NJ mouse has several distinct characteristics, such as large pronuclear morphology, vigorous reproductive performance, and consistently large litters that make it highly desirable for transgenic strain production and general purpose use.

Results: Using next-generation sequencing technology, we have sequenced the genome of FVB/NJ to approximately 50-fold coverage, and have generated a comprehensive catalog of single nucleotide polymorphisms, small insertion/deletion polymorphisms, and structural variants, relative to the reference C57BL/6J genome. We have examined a previously identified quantitative trait locus for atherosclerosis susceptibility on chromosome 10 and identify several previously unknown candidate causal variants.

Conclusion: The sequencing of the FVB/NJ genome and generation of this catalog has increased the number of known variant sites in FVB/NJ by a factor of four, and will help accelerate the identification of the precise molecular variants that are responsible for phenotypes observed in this widely used strain.

Figure 1

Distribution of SNPs, indels and structural variants in the FVB/NJ genome, relative to the reference C57BL/6J genome. Each rectangle represents a chromosome of the mouse genome. Shown in the top panel of each chromosome is the ideogram representation, followed by genome features, as indicated in the legend. SV, structural variant; TE, transposable element.

Figure 2

SNPs, indels, and structural variants (SVs) in the FVB/NJ mouse, in two narrowed regions of the chromosome 10 Ath11 locus. (a) The 10a locus from 1 to 7.3 Mb. (b) The 10b locus from 20.1 to 21.9 Mb. (c) Within the 10a region is the Mthdf1l gene, with non-synonymous and synonymous SNPs shown. Shown in red are non-synonymous SNPs or SNPs that affect intronic splice sites. In green are synonymous SNPs. In blue are gene models based on Ensembl version 64. Previously known FVB/NJ SNPs from dbSNP version 128 are also shown. The 10a region displayed in (a) begins at 3 Mb since the sequence from 1 bp to 3 Mb has not been assembled in the reference genome. Shown in the 10b region are the genes described in Wolfrum et al. [34] (Pde7b, Ahi1, Myb, Hbs1l, Aldh8a1, Sgk1), and additional predicted genes from Ensembl (1700020N01Rik, 1700021A07Rik, Gm5420, 4930444G20Rik, E030030I06Rik).