Sequencing and characterization of the FVB/NJ mouse genome

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.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.The origins of the FVB/NJ line can be traced back to an outbred colony of Swiss mice (N:GP, NIH general purpose) established at the National Institutes of Health (NIH) in the 1930s. A second colony (N:NIH) was subsequently established from the N:GP strain in the 1940s and then in the 1960s two new sub-lines (HSFS/N and HSFR/N) were established by selecting for sensitivity to histamine diphosphate challenge following pertussis vaccination. After eight generations of inbreeding, histamine-sensitive mice (HSFS/N) were found to carry the Fv-lb allele for sensitivity to the B strain of Friend leukemia virus [1,2]. These mice were bred to homozygosity and designated as the FVB/N inbred strain. FVB/N mice were imported to the Jackson Laboratories in 1988 at F37 and in 1991 were re-derived at N50 for addition to the Jackson foundation stocks. The FVB/NJ mouse has since become the workhorse of many mouse genetics laboratories due to its high reproductive performance, large litter sizes, and prominent pronuclei in fertilized eggs that make it an ideal strain for transgenic strain production [1,3]. FVB/NJ also represents an important disease model, and this strain has been used in a range of congenic and i