Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains

Abstract

Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse strains 129Sv (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from common ancestors within the last century1,2,3,4,5, yet very little is known about the genomic differences between them. By comparative genomic hybridization and sequence analysis of 129S5 short insert libraries, we identified substantial structural variation, a complex fine-scale haplotype pattern with a continuous distribution of diversity blocks, and extensive nucleotide variation, including nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes denote the level and direction of allele fixation that has occurred during inbreeding and provide a basis for defining what makes these mouse strains unique.

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Figure 1: CGH analysis of the C57BL/6J and 129S5 mouse genomes.
Figure 2: Refined haplotype structure of the mouse genome.
Figure 3: Analysis of diversity between strains 129S5 and C57BL/6J.

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GenBank/EMBL/DDBJ

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Acknowledgements

We thank B. Plumb and his team for sequencing; P. Biggs and members of the Sanger informatics team for their assistance; and W. Wang, L. van der Weyden, J. Jonkers and A. Velds for discussions. D.J.A. was supported by a CJ Martin Fellowship from the Australian National Health and Medical Research Council. This work was supported by the Wellcome Trust.

Author information

Correspondence to Allan Bradley.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Comparative genomic hybridisation of C57BL/6J and 129S5 genomes. (XLS 672 kb)

Supplementary Table 2

SNPs from this study that correspond to entries in dbSNP. (XLS 292 kb)

Supplementary Table 3

Synonymous and non- synonymous coding changes and stop codons. (XLS 547 kb)

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Adams, D., Dermitzakis, E., Cox, T. et al. Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains. Nat Genet 37, 532–536 (2005) doi:10.1038/ng1551

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