Mammalian Genome

, 17:417 | Cite as

Genetic characterization of a new set of recombinant inbred lines (LGXSM) formed from the intercross of SM/J and LG/J inbred mouse strains

  • Tomas Hrbek
  • Reinaldo Alves de Brito
  • B. Wang
  • L. Susan Pletscher
  • James M. Cheverud
Article

Abstract

A new set of LGXSM recombinant inbred (RI) strains is presented. The RI strain panel consists of 18 remaining strains of the original 55 founding strains. Strain characterization is based on 506 polymorphic microsatellites and 4289 single nucleotide polymorphisms (SNPs) distributed across the genome. Average microsatellite intermarker distance is 4.80 ± 4.84 Mb or 2.91 ± 3.21 F2 cM. SNPs are more densely spaced at 0.57 ± 1.27 Mb. Ninety-five percent of all microsatellite intermarker intervals are separated by less than 15.00 Mb or 8.50 F2 cM, while 95% of the SNPs are less than 0.95 Mb apart. Strains show expected low levels of nonsyntenic association among loci and complete genomic independence. During inbreeding, the RI strains went through strong natural selection on the agouti locus on Chromosome 2, especially when the epistatically interacting tyrosinase locus on Chromosome 7 carried the wild-type allele. The LG/J and SM/J strains differ in a large number of biomedically important traits, and they and their intercross progeny have been used in multiple mapping studies. The LG×SM RI strain panel provides a powerful new resource for mapping the genetic bases of complex traits and should prove to be of great biomedical utility in modeling complex human diseases such as obesity and diabetes.

Supplementary material

supp.pdf (310 kb)

References

  1. Akada JK, Ogura K, Dailidiene D, Dailide G, Cheverud JM, et al. (2003) Heliobacter pylori tissue tropism: Mouse colonizing strains can target different gastric niches. Microbiology 149:1901–1909CrossRefPubMedGoogle Scholar
  2. Brinkmann B, Klintschar M, Neuhuber F, Hühne J, Rolf B (1998) Mutation rate in human microsatellites: Influence of the structure and length of the tandem repeat. Am J Hum Genet 62:1408–1415CrossRefPubMedGoogle Scholar
  3. Chai C (1956a) Analysis of quantitative inheritance of body size in mice. I. Hybridization and maternal influence. Genetics 41: 157–164Google Scholar
  4. Chai C (1956b) Analysis of quantitative inheritance of body size in mice. II. Gene action and segregation. Genetics 41: 167–178Google Scholar
  5. Chai C (1957) Analysis of quantitative inheritance of body size in mice. III. Dominance. Genetics 42: 601–607PubMedGoogle Scholar
  6. Chai C (1961) Analysis of quantitative inheritance of body size in mice. IV. An attempt to isolate polygenes. Genet Res 2: 25–32CrossRefGoogle Scholar
  7. Chai C (1968) Analysis of quantitative inheritance of body size in mice. V. Effects of small numbers of polygenes on similar genetic backgrounds. Genet Res 11: 239–246PubMedGoogle Scholar
  8. Cheverud JM, Routman EJ, Duarte FAM, Van Swinderen B, Cothran K, et al. (1996) Quantitative trait loci for murine growth. Genetics 142: 1305–1319PubMedGoogle Scholar
  9. Cheverud JM, Routman EJ, Irschick DJ (1997) Pleiotropic effects of individual gene loci on mandibular morphology. Evolution 51: 2004–2014CrossRefGoogle Scholar
  10. Cheverud JM, Pletscher LS, Vaughn TT, Marshall B (1999a) Differential response to dietary fat in Large (LG/J) and Small (SM/J) inbred mouse strains. Physiol Genomics 1: 33–39Google Scholar
  11. Cheverud JM, Vaughn TT, Pletscher LS, King-Ellison K, Bailiff J, et al. (1999b) Epistasis and the evolution of additive genetic variance in populations that pass through a bottleneck. Evolution 53: 1009–1018CrossRefGoogle Scholar
  12. Cheverud JM, Vaughn TT, Pletscher LS, Peripato AC, Adams ES, et al. (2001) Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice. Mamm Genome 12: 3–12CrossRefPubMedGoogle Scholar
  13. Cheverud JM, Ehrich TH, Hrbek T, Kenney JP, Pletscher LS, et al. (2004a) Quantitative trait loci for obesity and diabetes-related traits and their dietary responses to a high fat diet in the LGXSM recombinant inbred mouse strains. Diabetes 53: 3328–3336Google Scholar
  14. Cheverud JM, Ehrich TH, Kenney JP, Pletscher LS, Semenkovich CF (2004b) Genetic evidence for discordance between obesity- and diabetes-related traits in the LGXSM recombinant inbred mouse strains. Diabetes 53: 2700–2708Google Scholar
  15. Cheverud JM, Ehrich TH, Vaughn TT, Koreishi SF, Linsey RB, et al. (2004c) Pleiotropic effects on mandibular morphology II. Differential epistasis and genetic variation in morphological integration. J Exp Zool Mol Dev Evol 302: 424–435CrossRefGoogle Scholar
  16. Crow JF, Kimura M (1970) An Introduction to Population Genetics Theory (Burgess Publishing: Minneapolis)Google Scholar
  17. Dietrich WF, Katz H, Lincoln SE (1992) A genetic map of the mouse suitable for typing in intraspecific crosses. Genetics 131: 423–447PubMedGoogle Scholar
  18. Ehrich TH, Kenney JP, Vaughn TT, Pletscher LS, Cheverud JM (2003a) Diet, obesity, and hyperglycemia in LG/J and SM/J mice. Obes Res 11: 1400–1410Google Scholar
  19. Ehrich TH, Vaughn TT, Koreishi SF, Linsey RB, Pletscher LS, et al. (2003b) Pleiotropic effects on mandibular morphology I. Developmental morphological integration and differential dominance. J Exp Zool Mol Dev Evol 269: 58–79CrossRefGoogle Scholar
  20. Ehrich TH, Hrbek T, Kenney-Hunt JP, Pletscher LS, Wang B, et al. (2005) Fine-mapping gene-by-diet interactions on Chromosome 13 in a LG/J × SM/J murine model of obesity. Diabetes 54: 1863–1872PubMedGoogle Scholar
  21. Eicher EM, Lee BK (1990) The NXSM recombinant inbred strains of mice: Genetic profile for 58 loci, including Mtv proviral loci. Genetics 125: 431–446PubMedGoogle Scholar
  22. Falconer DS, Mackay TFC (1996) Introduction to Quantitative Genetics, 4th ed. (Essex, UK: Longman)Google Scholar
  23. Festing MFW (1996) Origins and Characteristics of Inbred Strains of Mice. (New York: Oxford University Press)Google Scholar
  24. Frankel WN, Lee BK, Stoye JP, Coffin JM, Eicher EM (1992) Characterization of the endogenous nonecotropic murine leukemia viruses of NZB/B1NJ and SM/J inbred strains. Mamm Genome 2: 110–122CrossRefPubMedGoogle Scholar
  25. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, et al. (2002) The structure of haplotype blocks in the human genome. Science 296: 2225–2229CrossRefPubMedGoogle Scholar
  26. Goodale H (1938) A study of the inheritance of body weight in the albino mouse by selection. J Hered 29: 101–112Google Scholar
  27. Haldane JBS, Waddington CH (1931) Inbreeding and linkage. Genetics 16: 357–374PubMedGoogle Scholar
  28. Hanson WD (1959) The breakup of initial linkage blocks under selected mating systems. Genetics 44: 857–868PubMedGoogle Scholar
  29. Kayser M, Sajantila A (2001) Mutations at Y-STR loci: implications for paternity testing and forensic analysis. Forensic Sci Int 118: 116–121CrossRefPubMedGoogle Scholar
  30. Kenney-Hunt JP, Vaughn TT, Pletscher LS, Peripato A, Routman E, et al. (2006) Quantitative trait loci for body size components. Mamm Genome 17, in pressGoogle Scholar
  31. Klingenberg CP, Leamy LJ, Routman EJ, Cheverud JM (2001) Genetic architecture of mandible shape in mice: Effects of quantitative trait loci analyzed by geometric morphometrics. Genetics 157: 785–802PubMedGoogle Scholar
  32. Klingenberg CP, Leamy LJ, Cheverud JM (2004) Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics 166: 1909–1921CrossRefPubMedGoogle Scholar
  33. Kramer MG, Vaughn TT, Pletscher LS, King-Ellison K, Adams E, et al. (1998) Genetic variation in body weight gain and composition in the intercross of Large (LG/J) and Small (SM/J) inbred strains of mice. Genet Mol Biol 21: 211–218Google Scholar
  34. Leamy LJ, Routman EJ, Cheverud JM (1997) A search for quantitative trait loci affecting asymmetry of mandibular characters in mice. Evolution 51: 957–969CrossRefGoogle Scholar
  35. Leamy LJ, Routman EJ, Cheverud JM (1998) Quantitative trait loci for fluctuating asymmetry of discrete skeletal characters in mice. Heredity 80: 509–518CrossRefPubMedGoogle Scholar
  36. Leamy LJ, Routman EJ, Cheverud JM (1999) Quantitative trait loci for early- and late-developing skull characters in mice: A test of the genetic independence model of morphological integration. Am Nat 153: 201–214CrossRefGoogle Scholar
  37. Leamy LJ, Routman EJ, Cheverud JM (2002) An epistatic genetic basis for fluctuating asymmetry of mandible size in mice. Evolution 56: 642–653PubMedGoogle Scholar
  38. Leamy LJ, Workman MS, Routman EJ, Cheverud JM (2005) An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice. Heredity 94: 316-325CrossRefPubMedGoogle Scholar
  39. Liu S-C, Kowalski S, Lan T-H, Feldmann K, Paterson A (1996) Genome-wide high-resolution mapping by recurrent intermating using Arabidopsis thaliana as a model. Genetics 142: 247–258PubMedGoogle Scholar
  40. MacArthur J (1944) Genetics of body size and related characters. I. Selection of small and large races of the laboratory mouse. Am Nat 78: 42–157Google Scholar
  41. Mezey J, Cheverud JM, Wagner GP (2000) Is the genotype–phenotype map modular? A statistical approach using mouse QTL data. Genetics 156: 305–311PubMedGoogle Scholar
  42. Nishimura M, Hirayama N, Serikawa T, Kanehira K, Matsushima Y, et al. (1995) The SMXA: A new set of recombinant inbred strain of mice consisting of 26 substrains and their genetic profile. Mamm Genome 6: 850–587CrossRefPubMedGoogle Scholar
  43. Peripato AC, Cheverud JM (2002) Genetic influences on maternal care. Am Nat 160: s173–s185CrossRefPubMedGoogle Scholar
  44. Peripato AC, de Brito RA, Vaughn TT, Pletscher LS, Matioli SR, et al. (2002) Quantitative trait loci for maternal performance for offspring survival in mice. Genetics 162: 1341–1353PubMedGoogle Scholar
  45. Peripato AC, de Brito RA, Matioli SR, Pletscher LS, Vaughn TT, et al. (2004) Epistatis affecting litter size in mice. J Evol Biol 17: 593–602CrossRefPubMedGoogle Scholar
  46. Routman E, Cheverud J (1994) A rapid method of scoring simple sequence repeat polymorphisms with agarose gel electrophoresis. Mamm Genome 5: 187–188CrossRefPubMedGoogle Scholar
  47. Routman EJ, Cheverud JM (1995) Polymorphism for PCR-analyzed microsatellites between the inbred mouse strains LG and SM. Mamm Genome 6: 401–404CrossRefPubMedGoogle Scholar
  48. Routman EJ, Cheverud JM (1997) Gene effects on a quantitative trait: Two-locus epistatic effects measured at microsatellite markers and at estimated QTL. Evolution 51: 1654–1662CrossRefGoogle Scholar
  49. Sajantila A, Lukka M, Syvänen A-C (1999) Experimentally observed germline mutations at human micro- and minisatellite loci. Eur J Hum Genet 7: 263–266CrossRefPubMedGoogle Scholar
  50. Sokal RR, Rohlf FJ (1995) Biometry (W.H. Freeman and Co.: New York)Google Scholar
  51. Stickney HL, Schmutz J, Woods IG, Holtzer CC, Dickson MC, et al. (2002) Rapid mapping of zebrafish mutations with SNPs and oligonucleotide microarrays. Genome Res 12: 1929–1934CrossRefPubMedGoogle Scholar
  52. Taylor BA (1989) Recombinant inbred strains. In Lyon ML, Searle AG (eds.), Genetic Variants and Strains of the Laboratory Mouse, 2nd ed. (Oxford, UK: Oxford University Press), pp 773–796Google Scholar
  53. Templeton AR, Read B (1984) Factors eliminating inbreeding depression in a captive herd of Speke’s gazelle (Gazella spekei). Zoo Biol 3: 177–199CrossRefGoogle Scholar
  54. Vaughn TT, Pletscher LS, Peripato A, King-Ellison K, Adams E, et al. (1999) Mapping quantitative trait loci for murine growth: A closer look at genetic architecture. Genet Res 74: 313–322CrossRefPubMedGoogle Scholar
  55. Wade CM, Kulbokas EJ III, Kirby AW, Zody MC, Mullikin JC, et al. (2002) The mosaic structure of variation in the laboratory mouse genome. Nature 420: 574–578CrossRefPubMedGoogle Scholar
  56. Weber JL, Broman KW (2000) Genotyping for human whole-genome scans: past, present, and future. Adv Genet 42: 77–96CrossRefGoogle Scholar
  57. Weber JL, Wong CC (1993) Mutation of human short tandem repeats. Hum Mol Genet 2: 1123–1128PubMedGoogle Scholar
  58. Williams RW, Gu J, Qi S, Lu L (2001) The genetic structure of recombinant inbred mice: high-resolution consensus maps for complex trait analysis. Genome Res 2: 1–18Google Scholar
  59. Williams RW, Bennett B, Lu L, Gu J, DeFries JC, et al. (2004) Genetic structure of the L×S panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis. Mamm Genome 15: 637–647CrossRefPubMedGoogle Scholar
  60. Wolf JB, Vaughn TT, Pletscher LS, Cheverud JM (2002) Contribution of maternal effect QTL to genetic architecture of early growth in mice. Heredity 89: 300–310CrossRefPubMedGoogle Scholar
  61. Wolf JB, Leamy LJ, Routman EJ, Cheverud JM (2005) Epistatic pleiotropy and the genetic architecture of covariation within early- and late-developing skull trait complexes in mice. Genetics 171: 683-694CrossRefPubMedGoogle Scholar
  62. Workman MS, Leamy LJ, Routman EJ, Cheverud JM (2002) Analysis of QTL effects on the size and shape of mandibular molars in mice. Genetics 160: 1573–1586PubMedGoogle Scholar
  63. Wu R, Wang Z, Zhao W, Cheverud JM (2004) A mechanistic model for the genetic machinery of ontogenetic growth. Genetics 168: 2383–2394CrossRefPubMedGoogle Scholar
  64. Zhao W, Ma C-X, Cheverud JM, Wu R (2004) A unifying statistical model for QTL mapping of genotype-sex interaction for developmental trajectories. Physiol Genet 19: 218–277CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Tomas Hrbek
    • 1
  • Reinaldo Alves de Brito
    • 1
    • 2
  • B. Wang
    • 1
  • L. Susan Pletscher
    • 1
  • James M. Cheverud
    • 1
  1. 1.Department of Anatomy and NeurobiologyWashington University School of MedicineSt. LouisUSA
  2. 2.Departamento de Biologia Geral – ICBUniversidade Federal de São CarlosSão CarlosBrazil

Personalised recommendations