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Mammalian Genome

, Volume 16, Issue 12, pp 925–933 | Cite as

A catalog of nonsynonymous polymorphism on mouse Chromosome 16

  • Jeffrey M. Kidd
  • Karrie C. Trevarthen
  • David L. Tefft
  • Ze Cheng
  • Michaele Mooney
  • Mark D. AdamsEmail author
Article

Abstract

Numerous phenotypic traits differ among inbred mice, and the genetic diversity of inbred strains has been exploited in studies of quantitative trait loci (QTL). Sequencing the mouse genome has resulted in improved tools for the study of QTL, but a comprehensive catalog of sequence variants between strains would be of great value in identifying and testing potentially causative alleles. A/J DNA was included in the Celera shotgun sequence of the mouse genome and C57BL/6 DNA was sequenced by an international consortium. We have resequenced A/J and B6 DNA to cover nearly all of the protein-coding portions of mouse Chromosome 16, revealing that there are 106 nonsynonymous substitutions in 74 of the 779 genes on the chromosome. The pattern of substitution is more similar to the spectrum of benign polymorphism in the human population than it is to human disease-causing mutations. In mouse, polymorphic variants tend to be associated with one another on large haplotypes; this pattern also holds true for nonsynonymous polymorphism. However, sufficient fragmentation of haplotypes is present to suggest that only a very-high-resolution haplotype map will enable effective inference of alleles in additional strains.

Keywords

Quantitative Trait Locus Inbred Strain Inbred Mouse Strain Noncoding Sequence Nonsynonymous SNPs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors thank Courtney Bartel for assistance in verifying Celera SNPs. The location of A/J reads on Mmu16 was kindly provided by Celera Genomics.

References

  1. Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, et al. (2003) The nature and identification of quantitative trait loci: a community’s view. Nat Rev Genet 4: 911–916PubMedGoogle Scholar
  2. Adams DJ, Dermitzakis ET, Cox T, Smith J, Davies R, et al. (2005) Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains. Nat Genet 37: 532–536CrossRefPubMedGoogle Scholar
  3. Baroukh N, Ahituv N, Chang J, Shoukry M, Afzal V, et al. (2005) Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene. Mamm Genome 16: 91–95CrossRefPubMedGoogle Scholar
  4. Belknap JK (2003) Chromosome substitution strains: some quantitative considerations for genome scans and fine mapping. Mamm Genome 14: 723–732CrossRefPubMedGoogle Scholar
  5. Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, et al. (2004) Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res 14: 708–715PubMedGoogle Scholar
  6. Bogue M (2003) Mouse Phenome Project: understanding human biology through mouse genetics and genomics. J Appl Physiol 95: 1335–1337PubMedGoogle Scholar
  7. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, et al. (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36: 1133–1137CrossRefPubMedGoogle Scholar
  8. Dermitzakis ET, Reymond A, Lyle R, Scamuffa N, Ucla C, et al. (2002) Numerous potentially functional but non-genic conserved sequences on human chromosome 21. Nature 420: 578–582CrossRefPubMedGoogle Scholar
  9. Eppig JT, Bult CJ, Kadin JA, Richardson JE, Blake JA, et al. (2005) The Mouse Genome Database (MGD): from genes to mice—a community resource for mouse biology. Nucleic Acids Res 33: D471–475PubMedGoogle Scholar
  10. Festing MFW (1979) Inbred Strains in Biomedical Research (Oxford: Oxford University Press)Google Scholar
  11. Festing MFW (1996) Origins and characteristics of inbred strains of mice. In: Lyon M, Rastan S, Brown SDM (eds.)Genetic Variations and Strains of the Laboratory Mouse, (Oxford: Oxford University Press), pp 1537–1576Google Scholar
  12. Frazer KA, Wade CM, Hinds DA, Patil N, Cox DR,et al. (2004). Segmental phylogenetic relationships of inbred mouse strains revealed by fine-scale analysis of sequence variation across 4.6 mb of mouse genome. Genome Res 14: 1493–1500PubMedGoogle Scholar
  13. Gerlai R (2001) Eph receptors and neural plasticity. Nat Rev Neurosci 2: 205–209CrossRefPubMedGoogle Scholar
  14. Gerlai R (2002) EphB and NMDA receptors: components of synaptic plasticity coming together. Trends Neurosci 25: 180–181PubMedGoogle Scholar
  15. Gill KJ, Boyle AE (2003) Confirmation of quantitative trait loci for cocaine-induced activation in the AcB/BcA series of recombinant congenic strains. Pharmacogenetics 13: 329–338CrossRefPubMedGoogle Scholar
  16. Gill K, Desaulniers N, Desjardins P, Lake K (1998) Alcohol preference in AXB/BXA recombinant inbred mice: gender differences and gender-specific quantitative trait loci. Mamm Genome 9: 929–935CrossRefPubMedGoogle Scholar
  17. Gill K, Boyle A, Lake K, Desaulniers N (2000) Alcohol-induced locomotor activation in C57BL/6J, A/J, and AXB/BXA recombinant inbred mice: strain distribution patterns and quantitative trait loci analysis. Psychopharmacology (Berl) 150: 412–421Google Scholar
  18. Grubb SC, Churchill GA, Bogue MA (2004) A collaborative database of inbred mouse strain characteristics. Bioinformatics 20: 2857–2859CrossRefPubMedGoogle Scholar
  19. Hoogendoorn B, Coleman SL, Guy CA, Smith K, Bowen T, et al. (2003). Functional analysis of human promoter polymorphisms. Hum Mol Genet 12: 2249–2254CrossRefPubMedGoogle Scholar
  20. Korstanje R, Paigen B (2002) From QTL to gene: the harvest begins. Nat Genet 31: 235–236CrossRefPubMedGoogle Scholar
  21. Morse HC (1978) Origins of Inbred Mice. (New York: Academic Press), 719 ppGoogle Scholar
  22. Moses AM, Chiang DY, Pollard DA, Iyer VN, Eisen MB (2004) MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model. Genome Biol 5: R98CrossRefPubMedGoogle Scholar
  23. Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, et al. (2002) A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome. Science 296: 1661–1671CrossRefPubMedGoogle Scholar
  24. Ng PC, Henikoff S (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31: 3812–3814PubMedGoogle Scholar
  25. Pennacchio LA, Baroukh N, Rubin EM (2003) Human-mouse comparative genomics: successes and failures to reveal functional regions of the human genome. Cold Spring Harb Symp Quant Biol 68: 303–309CrossRefPubMedGoogle Scholar
  26. Poulin F, Nobrega MA, Plajzer-Frick I, Holt A, Afzal V, et al. (2005) In vivo characterization of a vertebrate ultraconserved enhancer. Genomics 85: 774–781CrossRefPubMedGoogle Scholar
  27. Ramensky V, Bork P, Sunyaev S (2002) Human non-synonymous SNPs: server and survey. Nucleic Acids Res 30: 3894–3900CrossRefPubMedGoogle Scholar
  28. Roper RJ, McAllister RD, Biggins JE, Michael SD, Min SH, et al. (2003) Aod1 controlling day 3 thymectomy-induced autoimmune ovarian dysgenesis in mice encompasses two linked quantitative trait loci with opposing allelic effects on disease susceptibility. J Immunol 170: 5886–5891PubMedGoogle Scholar
  29. Singer JB, Hill AE, Burrage LC, Olszens KR, Song J, et al. (2004) Genetic dissection of complex traits with chromosome substitution strains of mice. Science 304: 445–448CrossRefPubMedGoogle Scholar
  30. Tabakoff B, Bhave SV, Hoffman PL (2003) Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors. J Neurosci 23: 4491–4498PubMedGoogle Scholar
  31. Thomas JW, Touchman JW, Blakesley RW, Bouffard GG, Beckstrom-Sternberg SM, et al. (2003) Comparative analyses of multi-species sequences from targeted genomic regions. Nature 424: 788–793CrossRefPubMedGoogle Scholar
  32. Vitkup D, Sander C, Church GM (2003) The amino-acid mutational spectrum of human genetic disease. Genome Biol 4: R72CrossRefPubMedGoogle Scholar
  33. Wade CM, Kulbokas EJ 3rd, Kirby AW, Zody MC, Mullikin JC, et al. (2002) The mosaic structure of variation in the laboratory mouse genome. Nature 420: 574–578CrossRefPubMedGoogle Scholar
  34. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562PubMedGoogle Scholar
  35. Wiltshire T, Pletcher MT, Batalov S, Barnes SW, Tarantino LM, et al. (2003) Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse. Proc Natl Acad Sci U S A 100: 3380–3385CrossRefPubMedGoogle Scholar
  36. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Let al. (2005) Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434: 338–345PubMedGoogle Scholar
  37. Yalcin B, Fullerton J, Miller S, Keays DA, Brady S, et al. (2004) Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice. Proc Natl Acad Sci U S A 101: 9734–9739CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Jeffrey M. Kidd
    • 1
    • 4
  • Karrie C. Trevarthen
    • 1
  • David L. Tefft
    • 1
  • Ze Cheng
    • 1
    • 4
  • Michaele Mooney
    • 1
  • Mark D. Adams
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of GeneticsCase Western Reserve UniversityClevelandUSA
  2. 2.Center for Human GeneticsCase Western Reserve UniversityClevelandUSA
  3. 3.Center for Computational Genomics and Systems BiologyCase Western Reserve UniversityClevelandUSA
  4. 4.Department of Genome SciencesUniversity of WashingtonSeattleUSA

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