Genome Sequencing of Chromosome 1 Substitution Lines Derived from Chinese Wild Mice Revealed a Unique Resource for Genetic Studies of Complex Traits.
Mouse resources such as Collaborative Cross, outbred stocks, Hybrid Mouse Diversity Panel, and chromosome substitution strains have been instrumental to many progresses in the studies of complex traits genetics. We have established a population of chromosome 1 (Chr 1) substitution lines (C1SLs) in which donor chromosomes were derived from Chinese wild mice. Genome sequencing of 18 lines of this population showed that Chr 1 had been replaced by the donor chromosome. About 4.5 million unique single nucleotide polymorphisms and indels were discovered on Chr 1, of which 1.3 million were novel. Compared with sequenced classical inbred strains, Chr 1 of each C1SL had fivefold more variants, and more loss of function and potentially regulatory variants. Further haplotype analysis showed that the donor chromosome accumulated more historical recombination events, with the largest haplotype block being only 100 kb, and about 57% of the blocks were <1 kb. Subspecies origin analysis showed that these chromosomes had a mosaic genome structure that dominantly originated fromMus musculus musculusandM. m. castaneussubspecies, except for the C57BL/6J-Chr1KMline fromM. m. domesticusIn addition, phenotyping four of these lines on blood biochemistry suggested that there were substantial phenotypic variations among our lines, especially line C57BL/6J-Chr1HZand donor strain C57BL/6J. Further gene ontology enrichment revealed that the differentially expressed genes among liver-expressed genes between C57BL/6J and C57BL/6J-Chr1HZwere enriched in lipid metabolism biological processes. All these characteristics enable C1SLs to be a unique resource for identifying and fine mapping quantitative trait loci on mouse Chr 1, and carrying out systems genetics studies of complex traits.
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Fuyi
http://orcid.org/0000-0002-5952-5771
F
Xu
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Tianzhu
T
Chao
The Laboratory of Genetic Regulators in the Immune System, Xinxiang Medical University, Henan 453003, China.
Yingming
Y
Liang
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Kai
K
Li
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Shixian
S
Hu
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Maochun
M
Wang
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China.
Yuxun
Y
Zhou
Department of Biostatistics and Epidemiology, Medical College of Georgia, Augusta University, Georgia 30912 hxu@augusta.edu xiaojunhua@dhu.edu.cn.
Hongyan
H
Xu
College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai 201620, China hxu@augusta.edu xiaojunhua@dhu.edu.cn.
Junhua
J
Xiao
Chinese wild mice; chromosome substitution; genetic polymorphisms; haplotype; whole genome sequencing