Advertisement

QTL Mapping of Behaviour in the Zebrafish

  • Dominic Wright
Protocol
  • 1k Downloads
Part of the Neuromethods book series (NM, volume 52)

Abstract

The study of complex traits is one of the greatest current challenges in biology, and the exact mechanism whereby individual genes cause small quantitative variation in any given trait still remains largely unresolved. In the case of behavioural traits, with lower heritabilities and repeatabilities as compared to other character-types, this problem is exacerbated even further. One of the principal forms of genetic analysis for quantitative traits is via QTL (quantitative trait loci) mapping, with the power of this approach even greater in model organisms due to the array of genomic tools available. These tools give a genuine possibility of identifying the actual causative genes or nucleotides responsible for the variation (the quantitative trait nucleotide, or QTN). The zebrafish displays a range of behaviours that are both complex and bear a striking similarity to some of the behavioural measurements performed in other model organisms, notably affecting anxiety and social aggregation. The combination of the behavioural variation present in the zebrafish and the genetic and genomic advantages to QTL mapping available for this species paves the way for its use in generating a new model for the genetic dissection of such trait types. This chapter aims to first discuss the zebrafish as a behavioural model suitable for QTL mapping, focussing in particular on the behaviours of shoaling and predator inspection, before giving an overview of what is contained in a QTL study and the types of crossings, analysis and their relevance to behavioural QTL mapping. Finally two case studies are presented, one of anxiety behaviour in mice, one of shoaling and boldness behaviour in zebrafish.

Key words

Genetic analysis behavioural genetics quantitative trait loci mapping quantitative trait nucleotide population differences domestication anxiety shoaling behaviour behaviour variation single nucleotide polymorphism oligonucleotide array predator inspection environment variation bioinformatics 

References

  1. 1.
    Barton, N. H. & Keightley, P. D. (2002) Understanding quantitative genetic variation. Nat Rev Genet 3, 11–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Falconer, D. S. & Mackay, T. F. C. (1996) Introduction to Quantitative Genetics. Upper Saddle River, NJ, Prentice Hall.Google Scholar
  3. 3.
    Lander, E. S. & Botstein, D. (1989) Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.PubMedGoogle Scholar
  4. 4.
    Mehrabian, M., Allayee, H., Stockton, J., Lum, P. Y., Drake, T. A., Castellani, L. W., Suh, M., Armour, C., Edwards, S., Lamb, J., Lusis, A. J. & Schadt, E. E. (2005) Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Nat Genet 37, 1224–1233.PubMedCrossRefGoogle Scholar
  5. 5.
    Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K., Yoshimura, T., Nabeshima, T. & Ebihara, S. (2009) Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nat Genet 41, 688–695.PubMedCrossRefGoogle Scholar
  6. 6.
    van Laere, A. S., Nguyen, M., Braunschweig, M., Nezer, C., Collette, C., Moreau, L., Archibald, A., Haley, C. S., Buys, N., Tally, M., Andersson, G., Georges, M. & Andersson, L. (2003) A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in pigs. Nature 425, 832–836.PubMedCrossRefGoogle Scholar
  7. 7.
    Bolivar, V., Cook, M. & Flaherty, L. (2000) List of transgenic and knockout mice: behavioural profiles. Mammal Genome 11, 260–274.CrossRefGoogle Scholar
  8. 8.
    Flint, J. (1999) The genetic basis of cognition. Brain 122, 2015–2032.PubMedCrossRefGoogle Scholar
  9. 9.
    Flint, J. (2003) Analysis of quantitative trait loci that influence animal behaviour. J Neurobiol 54, 46–77.PubMedCrossRefGoogle Scholar
  10. 10.
    de Bono, M. & Bargmann, C. I. (1998) Natural variation in a neuropeptide y receptor homolog modifies social behavior and food response in C. elegans. Cell 94, 679–689.PubMedCrossRefGoogle Scholar
  11. 11.
    Osborne, K. A., Robichon, A., Burgess, E., Butland, S., Shaw, R. A., Coulthard, A., Pereira, H. S., Greenspan, R. J. & Sokolowksi, M. B. (1997) Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila. Science 277, 834–836.PubMedCrossRefGoogle Scholar
  12. 12.
    Shimoda, N., Knapik, E. W., Ziniti, J., Sim, C., Yamada, E., Kaplan, S., Jackson, D., de Sauvage, F., Jacob, H. & Fishman, M. C. (1999) Zebrafish genetic map with 2000 microsatellite markers. Genomics 58, 219–232.PubMedCrossRefGoogle Scholar
  13. 13.
    Gratton, P. et al. (2004) Allozyme and microsatellite genetic variation in natural samples of zebrafish, Danio rerio. J Zoolog Syst Evol Res 42, 54–62.CrossRefGoogle Scholar
  14. 14.
    Guryev, V. et al. (2006) Genetic variation in the zebrafish. Genome Res 16, 491–496.PubMedCrossRefGoogle Scholar
  15. 15.
    Gerlach, G. & Lysiaki, N. (2006) Kin recognition and inbreeding avoidance in the zebrafish, Danio rerio, is based on phenotype matching. Anim Behav 71, 1371–1377.CrossRefGoogle Scholar
  16. 16.
    Bloom, H. D. & Perlmutter, A. (1977) A sexual aggregating pheromone system in the zebrafish Brachydanio rerio. J Exp Zool 199, 215–226.PubMedCrossRefGoogle Scholar
  17. 17.
    Bloom, H. D. & Perlmutter, A. (1978) Possible pheromone mediated reproductive isolation in two species of cyprinid fish of the genus, brachydanio. J Fish Biol 13, 47–50.CrossRefGoogle Scholar
  18. 18.
    Spence, R. & Smith, C. (2006) Mating preference of female zebrafish, Danio rerio, in relation to male dominance. Behav Ecol 17, 779–783.CrossRefGoogle Scholar
  19. 19.
    Engeszer, R. & Ryan, M. J. (2004) Learned social preference in zebrafish. Curr Biol 14, 881–884.PubMedCrossRefGoogle Scholar
  20. 20.
    McCann, L. I., Koehn, D. J. & Kline, N. J. (1971) The effects of body size and body markings on nonpolarized schooling behaviour of zebrafish (Brachydanio rerio). J Psychol 79, 71–75.PubMedCrossRefGoogle Scholar
  21. 21.
    McCann, L. I. & Matthews, J. J. (1974) The effects of lifelong isolation on species identification in zebrafish (Brachydanio rerio). Dev Psychobiol 7, 159–163.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenthal, G. G. & Ryan, M. J. (2005) Assortative preference for stripes in danios. Anim Behav 70, 1063–1066.CrossRefGoogle Scholar
  23. 23.
    Pritchard, V. L., Lawrence, J., Butlin, R. K. & Krause, J. (2001) Shoal choice in zebrafish (Danio rerio): the influence of shoal size and activity. Anim Behav 62.Google Scholar
  24. 24.
    Bass, S. & Gerlach, R. (2008) Zebrafish (Danio rerio) responds differentially to stimulus fish: the effects of sympatric and allopatric predators and harmless fish. Behav Brain Res 186, 107–117.PubMedCrossRefGoogle Scholar
  25. 25.
    Oswald, M. & Robison, B. D. (2008) Strain-specific alteration of zebrafish feeding behavior in response to aversive stimuli. Can J Zool 86, 1085–1094.PubMedCrossRefGoogle Scholar
  26. 26.
    Pitcher, T. J. (1983) Heuristic definitions of fish shoaling behaviour. Anim Behav 31, 611–612.CrossRefGoogle Scholar
  27. 27.
    Krause, J. & Ruxton, G. (2002) Living in Groups. Oxford, Oxford University Press.Google Scholar
  28. 28.
    Pavlov, D. S. & Kasumyan, A. O. (2000) Patterns and mechanisms of schooling behavior in fish: a review. J Ichthyol 40, 163–231.Google Scholar
  29. 29.
    Wright, D., Ward, A. J. W., Croft, D. P. & Krause, J. (2006d) Social organization, grouping, and domestication in fish. Zebrafish 3, 141–156.PubMedCrossRefGoogle Scholar
  30. 30.
    Pitcher, T. J. (1992) Who dares wins: the function and evolution of predator inspection behaviour in fish shoals. Neth J Zool 42, 371–391.CrossRefGoogle Scholar
  31. 31.
    Magurran, A. E. & Pitcher, T. J. (1987) Provenance, shoal size and the sociobiology of predator-evasion behavior in minnow shoals. Proc R Soc Lond B 229, 439–465.CrossRefGoogle Scholar
  32. 32.
    Pitcher, T. J. & Parrish, J. K. (1993) Functions of shoaling behaviour in teleosts. In Pitcher, T. J. (Ed.) Behaviour of Teleost Fishes. 2nd ed. London, Chapman and Hall.CrossRefGoogle Scholar
  33. 33.
    Magurran, A. E. (1990) The inheritance and development of minnow antipredator behavior. Anim Behav 39, 834–842.CrossRefGoogle Scholar
  34. 34.
    Magurran, A. E., Seghers, B. H., Shaw, P. W. & Carvalho, G. R. (1995) The behavioural diversity and evolution of guppy. Poecilia reticulata. Populations in Trinidad. Advances in the Study of Behavior. San Diego, CA, Academic Press Inc.Google Scholar
  35. 35.
    Wright, D., Rimmer, L. B., Pritchard, V. L., Krause, J. & Butlin, R. K. (2003) Inter and intra-population variation in shoaling and boldness in the zebrafish (Danio rerio). Naturwissenschaften 90, 374–377.PubMedCrossRefGoogle Scholar
  36. 36.
    Wright, D. & Krause, J. (2006) Repeated measures of shoaling tendency in zebrafish (Danio rerio) and other small teleost fishes. Nat Protocols 1, 1828–1831.CrossRefGoogle Scholar
  37. 37.
    Ruzzante, D. E. & Doyle, R. W. (1991) Rapid behavioral-changes in medaka (oryzias-latipes) caused by selection for competitive and noncompetitive growth. Evolution 45, 1936–1946.CrossRefGoogle Scholar
  38. 38.
    Ruzzante, D. E. & Doyle, R. W. (1993) Evolution of social-behavior in a resource-rich, structured environment – election experiments with medaka (Oryzias-Latipes). Evolution 47, 456–470.CrossRefGoogle Scholar
  39. 39.
    Dugatkin, L. A., McCall, M. A., Gregg, R. G., Cavanaugh, A., Christensen, C. & Unseld, M. (2005) Zebrafish (Danio rerio) exhibit individual differences in risk-taking behavior during predator inspection. Ethol Ecol Evol 17, 77–81.CrossRefGoogle Scholar
  40. 40.
    Lynch, M. & Walsh, B. (1998) Genetics and Analysis of Quantitative Traits. Sunderland, MA, Sunderland Sinauer Associates.Google Scholar
  41. 41.
    Kerje, S., Carlborg, O., Jacobsson, L., Schutz, K., Hartmann, C., Jensen, P. & Andersson, L. (2003) The twofold difference in adult size between the red junglefowl and White Leghorn chickens is largely explained by a limited number of QTLs. Anim Genet 34, 264–274.PubMedCrossRefGoogle Scholar
  42. 42.
    Wright, D., Kerje, S., Brändström, H., Schütz, K., Kindmark, A., Andersson, L., Jensen, P. & Pizzari, T. (2008) The genetic architecture of a female sexual ornament. Evolution 62, 86–98.PubMedCrossRefGoogle Scholar
  43. 43.
    Wright, D., Kerje, S., Lundström, K., Babol, J., Schutz, K., Jensen, P. & Andersson, L. (2006b) Quantitative trait loci analysis of egg and meat production traits in a red junglefowl × white leghorn cross. Anim Genet 37, 529–534.PubMedCrossRefGoogle Scholar
  44. 44.
    Buitenhuis, A. J., Rodenburgb, T. B., Siweka, M., Cornelissena, S. J. B., Nieuwland, M. G. B., Crooijmansa, R. P. M. A., Groenen, M. A. M., Koene, P., Bovenhuis, H. & van der Poel, J. J. (2004) Quantitative trait loci for behavioural traits in chickens. Livestock Product Sci 93, 95–103.CrossRefGoogle Scholar
  45. 45.
    Schutz, K., Kerje, S., Carlborg, O., Jacobsson, L., Andersson, L. & Jensen, P. (2002) QTL analysis of a red junglefowl × white leghorn intercross reveals trade-off in resource allocation between behavior and production traits. Behav Genet 32, 423–433.PubMedCrossRefGoogle Scholar
  46. 46.
    Schutz, K. E., Kerje, S., Jacobsson, L., Forkman, B., Carlborg, O., Andersson, L. & Jensen, P. (2004) Major growth QTLs in fowl are related to fearful behavior: possible genetic links between fear responses and production traits in a red junglefowl × white leghorn intercross. Behav Genet 34, 121–130.PubMedCrossRefGoogle Scholar
  47. 47.
    Price, E. O. (1984) Behavioral aspects of animal domestication. Quart Rev Biol 59, 1–32.CrossRefGoogle Scholar
  48. 48.
    Darwin, C. (1859) The Origin of Species. New York, NY, Mentor.Google Scholar
  49. 49.
    Darwin, C. (1868) The Variation of Animals and Plants Under Domestication. London, John Murray.Google Scholar
  50. 50.
    Ochieng-Odero, J. P. R. (1994) Does adaptation occur in insect rearing systems, or is it a case of selection, acclimatization and domestication? Insect Sci Appl 15, 1–7.Google Scholar
  51. 51.
    Price, E. O. (1999) Behavioral development in animals undergoing domestication. Appl Anim Behav Sci 65, 245–271.CrossRefGoogle Scholar
  52. 52.
    Kallio-Nyberg, I., Salminen, M., Saloniemi, I. & Kannala-Fisk, L. (2009) Marine survival of reared Atlantic salmon in the Baltic Sea: the effect of smolt traits and annual factors. Fish Res 96, 289–295.CrossRefGoogle Scholar
  53. 53.
    Olla, B. L. & Davis, M. W. (1989) The role of learning and stress in predator avoidance of hatchery and wild steelhead trout. Aquaculture 76, 209–214.CrossRefGoogle Scholar
  54. 54.
    Lucas, M. D., Drew, R. E., Wheeler, P. A., Verrell, P. A. & Thorgaard, G. H. (2004) Behavioral differences among rainbow trout clonal lines. Behav Genet 34, 355–365.PubMedCrossRefGoogle Scholar
  55. 55.
    Berejikian, B. A. (1995) The effects of hatchery and wild ancestry and experience on the relative ability of steelhead trout fry (oncorhynchus mykiss) to avoid a benthic predator. Can J Fish Aquat Sci 52, 2476–2482.CrossRefGoogle Scholar
  56. 56.
    Johnsson, J., Petersson, E., Jonsson, E., Bjornsson, B. & Jarvi, T. (1996) Domestication and growth hormone alter antipredator behaviour and growth patterns in juvenile brown trout, Salmo trutta. Can J Fish Aquat Sci 53, 1546–1554.CrossRefGoogle Scholar
  57. 57.
    Swain, D. P. & Riddell, B. E. (1990) Variation in agonistic behavior between newly emerged juveniles from hatchery and wild populations of coho salmon. Can J Fish Aquat Sci 47, 566–571.CrossRefGoogle Scholar
  58. 58.
    Fleming, I. A. & Einum, S. (1997) Experimental tests of genetic divergence of farmed from wild Atlantic salmon due to domestication. ICES J Marine Sci 54, 1051–1063.Google Scholar
  59. 59.
    Price, E. O. & King, J. A. (1968) Domestication and adaptation. In Hafez, E. S. E. (Ed.) Adaptation of Domestic Animals. Philadelphia, PA, Lea and Febiger.Google Scholar
  60. 60.
    Fevolden, S. E., Refstie, T. & Roed, K. H. (1991) Selection for high and low cortisol stress response in Atlantic salmon (Salmo salar) and rainbow-trout (Oncorhynchus mykiss). Aquaculture 95, 53–65.CrossRefGoogle Scholar
  61. 61.
    Spurway, H. (1955) The causes of domestication: an attempt to integrate some ideas of Konrad Lorenz with evolution theory. J Genet 53, 325–362.CrossRefGoogle Scholar
  62. 62.
    Robison, B. D. & Rowland, W. (2005) A potential model system for studying the genetics of domestication: behavioral variation among wild and domesticated strains of zebrafish (Danio rerio). Can J Fish Aquat Sci 62, 2046–2054.CrossRefGoogle Scholar
  63. 63.
    Moretz, J. A., Martins, E. P. & Robison, B. D. (2007) Behavioral syndromes and the evolution of correlated behavior in zebrafish. Behav Ecol 18, 556–562.CrossRefGoogle Scholar
  64. 64.
    Darvasi, A. (1998) Experimental strategies for the genetic dissection of complex traits in animal models. Nat Genet 18, 19–24.PubMedCrossRefGoogle Scholar
  65. 65.
    Lander, E. S. & Kruglyak, L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11, 241–247.PubMedCrossRefGoogle Scholar
  66. 66.
    Williams, R. W., Gu, J., Qi, S. & Lu, L. (2001) The genetic structure of recombinant inbred mice: high-resolution consensus maps for complex trait analysis. Genome Biol 2, 1–18.Google Scholar
  67. 67.
    Belknap, J. K., Mitchel, S. R. & Crabbe, J. C. (1996) Type I and type ii error rates for quantitative trait loci (QTL) mapping studies using inbred mouse strains: computer simulation and empirical results. Behav Genet 26, 149–160.PubMedCrossRefGoogle Scholar
  68. 68.
    Darvasi, A. & Soller, M. (1995) Advanced intercross lines, an experimental population for fine genetic-mapping. Genetics 141, 1199–1207.PubMedGoogle Scholar
  69. 69.
    Peirce, J. L., Broman, K. W., Lu, L., Chesler, E. J., Zhou, G., Airey, D. C., Birmingham, A. E. & Williams, R. W. (2008) Genome reshuffling for advanced intercross permutation (graip): simulation and permutation for advanced intercross population analysis. PLoS One 3, e1977.PubMedCrossRefGoogle Scholar
  70. 70.
    Haldane, J. B. S. (1919) The combination of linkage values, and the calculation of distance between the loci of linked factors. J Genet 8, 299–309.CrossRefGoogle Scholar
  71. 71.
    Kosambi, D. D. (1944) The estimation of map distances from recombination values. Ann Eugen 12, 172–175.Google Scholar
  72. 72.
    Weeks, D. E. & Lange, K. (1987) Preliminary ranking procedures for multilocus ordering. Genomics 1, 236–242.PubMedCrossRefGoogle Scholar
  73. 73.
    Buetow, K. H. & Chakravarti, A. (1987) Multipoint gene mapping using seriation. I. General methods. Am J Hum Genet 41, 180–188.PubMedGoogle Scholar
  74. 74.
    Thompson, E. A. (1987) Crossover counts and likelihood in multipoint linkage analysis. Math Med Biol 4, 93–108.CrossRefGoogle Scholar
  75. 75.
    Doerge, R. W. (1996) Constructing genetic maps by rapid chain delineation. J Quant Trait Loci 2, Article 6.Google Scholar
  76. 76.
    Doerge, R. W. (2002) Mapping and analysis of quantitative trait loci in experimental populations. Nat Rev Genet 3, 43–52.PubMedCrossRefGoogle Scholar
  77. 77.
    Martinez, O. & Curnow, R. N. (1992) Estimating the locations and size of effects of quantitative trait loci using flanking markers. Theor Appl Genet 85, 480–488.CrossRefGoogle Scholar
  78. 78.
    Haley, C. S. & Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.PubMedCrossRefGoogle Scholar
  79. 79.
    Haley, C. S., Knott, S. A. & Elsen, J. M. (1994) Mapping quantitative trait loci in crosses between outbred lines using least squares. Genetics 136, 1195–1207.PubMedGoogle Scholar
  80. 80.
    Piepho, H. P. & Gauch, H. G. (2001) Marker pair selection for mapping quantitative trait loci. Genetics 157, 433–444.PubMedGoogle Scholar
  81. 81.
    Kao, C. -H., Zeng, Z. -B. & Teasdale, R. D. (1999) Multiple interval mapping for quantitative trait loci. Genetics 152, 1203–1216.PubMedGoogle Scholar
  82. 82.
    Churchill, G. A. & Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 964–971.Google Scholar
  83. 83.
    Doerge, R. W. & Churchill, G. A. (1996) Permutation tests for multiple loci affecting a quantitative character. Genetics 142, 285–294.PubMedGoogle Scholar
  84. 84.
    Benjamini, Y. & Yekutieli, D. (2005) Quantitative trait loci analysis using the false discovery rate. Genetics 171, 783–790.PubMedCrossRefGoogle Scholar
  85. 85.
    Beavis, W. D. (1998) QTL analyses: power, precision and accuracy. Proceedings of the 49th Annual Corn and Sorghum Industry Research Conference. Washington, DC, ASTA.Google Scholar
  86. 86.
    Belknap, J. K. & Atkins, A. L. (2001) The replicabilitity of QTLs for murine alcohol preference drinking behavior across eight independent studies. Mammal Genome 12, 893–899.CrossRefGoogle Scholar
  87. 87.
    Turri, M. G., Henderson, N. D., Defries, J. C. & Flint, J. (2001) Quantitative trait locus mapping in laboratory mice derived from a replicated selection experiment for open-field activity. Genetics 158, 1217–1226.PubMedGoogle Scholar
  88. 88.
    Hitzemann, R., Cipp, L., Demarest, K., Mahjubi, E. & McCaughran, J. J. (1998) Genetics of ethanol-induced locomotor activation: detection of QTLs in a C57BL/6 J × DBA/2 J F2 intercross. Mammal Genome 9, 956–962.CrossRefGoogle Scholar
  89. 89.
    Risch, N. & Botstein, D. (1996) A manic depressive history. Nat Genet 12, 351–353.PubMedCrossRefGoogle Scholar
  90. 90.
    Crabbe, J. C., Philips, T. J., Buck, K. J., Cunningham, C. L. & Belknap, J. K. (1999a) Identifying genes for alcohol and drug sensitivity: recent progress and future directions. Trends Neurosci 22, 173–179.PubMedCrossRefGoogle Scholar
  91. 91.
    Flint, J., Corley, J. C., Defries, J. C., Fulker, D. W. & Gray, J. A. (1995) A simple genetic basis for a complex psychological trait in laboratory mice. Science 269, 1432–1435.PubMedCrossRefGoogle Scholar
  92. 92.
    Moisan, M. P., Courvoisier, H., Bihoreau, M. T., Bgaugier, D., Hendley, E. D., Lathrop, M., James, M. R. & Mormede, P. (1996) A major quantitative trait locus influences hyperactivity in the Wkha rat. Nat Genet 14, 471–473.PubMedCrossRefGoogle Scholar
  93. 93.
    Otto, S. P. & Jones, C. D. (2000) Detecting the undetected: estimating the total number of loci underlying a quantitative trait. Genetics 156, 2093–2107.PubMedGoogle Scholar
  94. 94.
    Mousseau, T. A. & Roff, D. A. (1987) Natural-selection and the heritability of fitness components. Heredity 59, 181–197.PubMedCrossRefGoogle Scholar
  95. 95.
    Hill, W. G., Goddard, M. E. & Visscher, P. M. (2008) Data and theory point mainly to additive genetic variance for complex traits. PLoS Genet 4(2), e1000008.PubMedCrossRefGoogle Scholar
  96. 96.
    Cockerham, C. C. & Zeng, Z. -B. (1996) Design III with marker loci. Genetics 143, 1437–1456.PubMedGoogle Scholar
  97. 97.
    Damerval, C., Maurice, A., Josse, J. M. & de Vienne, D. (1994) Quantitative trait loci underlying gene product variation: a novel perspective by analyzing regulation of genome expression. Genetics 137, 289–301.PubMedGoogle Scholar
  98. 98.
    Doebley, J., Stec, A. & Gustus, C. (1995) Teosinte branched1 and the origin of maze: evidence for epistasis and the evolution of dominance. Genetics 141, 333–346.PubMedGoogle Scholar
  99. 99.
    Carlborg, O. & Haley, C. S. (2004) Epistasis: too often neglected in complex trait studies? Nat Rev Genet 5, 618–625.PubMedCrossRefGoogle Scholar
  100. 100.
    Carlborg, O., Jacobsson, L., Ahgren, P., Siegel, P. & Andersson, L. (2006) Epistasis and the release of genetic variation in response to selection. Nat Genet 38, 418–420.PubMedCrossRefGoogle Scholar
  101. 101.
    Carlborg, O., Kerje, S., Schutz, K., Jacobsson, L., Jensen, P. & Andersson, L. (2003) A global search reveals epistatic interaction between QTL for early growth in the chicken. Genome Res 13, 413–421.PubMedCrossRefGoogle Scholar
  102. 102.
    Routman, E. J. & Cheverud, J. M. (1997) Gene effects on a quantitative trait: two-locu epistatic effects measured at microsatellite markers and at estimated QTL. Evolution 51, 1654–1662.CrossRefGoogle Scholar
  103. 103.
    Peripato, A. C., de Brito, R. A., Matioloi, S. R., Pletscher, L. S., Vaughn, T. T. & Cheverud, J. M. (2004) Epistasis affecting litter size in mice. J Evol Biol 17, 593–602.PubMedCrossRefGoogle Scholar
  104. 104.
    Shook, D. R. & Johnson, T. E. (1999) Quantitative trait loci affecting survival and fertility-related traits in Caenorhabditis elegans show genotype-environment interactions, pleiotropy and epistasis. Genetics 153, 1233–1243.PubMedGoogle Scholar
  105. 105.
    Malmberg, R. L. & Mauricio, R. (2005) QTL-based evidence for the role of epistasis in evolution. Genet Res Camb 86, 89–95.CrossRefGoogle Scholar
  106. 106.
    Hood, H. M., Belknap, J. K., Crabbe, J. C. & Buck, K. J. (2001) Genomewide search for epistasis in a complex trait: pentobarbital withdrawal convulsions in mice. Behav Genet 31, 93–100.PubMedCrossRefGoogle Scholar
  107. 107.
    Anholt, R. R. H., Dilda, C. L., Chang, S., Fanara, J. -J., Kulkarni, N. H., Ganguly, I., Rollman, S. M., Kamdar, K. P. & Mackay, T. F. C. (2003) The genetic architecture of odor-guided behaviour in Drosophila: epistasis and the transcriptome. Nat Genet 35, 180–184.PubMedCrossRefGoogle Scholar
  108. 108.
    Anholt, R. R. H., Lyman, R. F. & Mackay, T. F. C. (1996) Effects of single P-element insertions on olfactory behavior in Drosophila melanogaster. Genetics 143, 293–301.PubMedGoogle Scholar
  109. 109.
    Fedorowicz, G. M., Fry, J. D., Anholt, R. R. H. & Mackay, T. F. C. (1998) Epistatic interactions between smell-impaired loci in Drosophila melanogaster. Genetics 148, 1885–1891.PubMedGoogle Scholar
  110. 110.
    Ruppell, O., Pankiw, T. & Page, R. E., Jr. (2004) Pleiotropy, epistasis and new QTL: the genetic architecture of honey bee foraging behavior. J Heredity 96, 481–491.CrossRefGoogle Scholar
  111. 111.
    Wright, D., Butlin, R. K. & Carlborg, Ö. (2006a) Epistatic regulation of behavioural and morphological traits in the zebrafish (Danio rerio). Behav Genet 36, 914–922.PubMedCrossRefGoogle Scholar
  112. 112.
    Flint, J., Defries, J. C. & Henderson, N. D. (2004) Little epistasis for anxiety-related measures in the DeFries strains of laboratory mice. Mammal Genome 15, 77–82.CrossRefGoogle Scholar
  113. 113.
    Sen, S. & Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.PubMedGoogle Scholar
  114. 114.
    Melo, J. A., Sjendure, J., Pociask, K. & Silver, L. M. (1996) Identification of sex-specific quantitative trait loci controlling alcohol preference in C57BL/6 mice. Nat Genet 13, 147–153.PubMedCrossRefGoogle Scholar
  115. 115.
    Gershenfeld, H. K. & Paul, S. M. (1997) Mapping quantitative trait loci for fear-like behaviors in mice. Genomics 46, 1–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Crabbe, J. C., Wahlsten, D. & Dudek, B. C. (1999b) Genetics of mouse behavior: interactions with laboratory environment. Science 284, 1670–1672.PubMedCrossRefGoogle Scholar
  117. 117.
    Pellow, S., Chopin, P., File, S. & Briley, M. (1985) Validation of open:closed arms entries in an elevated plus maze as a measure of anxiety in the rat. J Neurosci Methods 14, 149–167.PubMedCrossRefGoogle Scholar
  118. 118.
    File, S. E., Mabbutt, P. S. & Hitchcott, P. K. (1990) Characterisations of the phenomenon of “one-trial tolerance” to the anxiolytic effect of chlordiazepoxide in the elevated plus maze. Psychopharmacology 102, 98–101.PubMedCrossRefGoogle Scholar
  119. 119.
    Dawson, G. R., Crawford, S. P., Collinson, N. & Iversen, S. D. (1995) Evidence that the anxiolytic-like effects of chlordiazepoxide on the elevated-plus maze are confounded by increases in locomotor-activity. Psychopharmacology 118, 316–323.PubMedCrossRefGoogle Scholar
  120. 120.
    Mather, K. & Jinks, J. L. (1982) Biometrical Genetics. Cambridge, Chapman and Hall.Google Scholar
  121. 121.
    Mott, R. & Flint, J. (2002) Simultaneous detection and fine mapping of quantitative trait loci in mice using heterogeneous stocks. Genetics 160, 1609–1618.PubMedGoogle Scholar
  122. 122.
    Talbot, C. J., Radcliffe, R. A., Fullerton, J., Hitzemann, R., Wehner, J. M. & Flint, J. (2003) Fine scale mapping of a genetic locus for conditioned fear. Mammal Genome 14, 223–230.CrossRefGoogle Scholar
  123. 123.
    Flint, J. & Mott, R. (2001) Finding the molecular basis of quantitative traits: successes and pitfalls. Nat Rev Genetics 2(6), 437–445.CrossRefGoogle Scholar
  124. 124.
    Breese, E. L. & Mather, K. (1957) The organization of polygenic activity within a chromosome in Drosophila: 1. Hair characters. Heredity 11, 373–395.CrossRefGoogle Scholar
  125. 125.
    Shrimpton, A. E. & Robertson, A. (1988) The isolation of factors controlling bristle score in Drosophila melanogaster: I. allocation of third chromosome sternopleural bristle effects to chromosome sections. Genetics 118, 437–443.PubMedGoogle Scholar
  126. 126.
    Darvasi, A. (1997) Interval-specific congenic strains (iscs): an experimental design for mapping a QTL into a 1-centimorgan interval. Mammal Genome 8, 163–167.CrossRefGoogle Scholar
  127. 127.
    Valdar, W., Solberg, L. C., Gauguier, D., Burnett, S., Klenerman, P., Cookson, W. O., Taylor, M. S., Rawlins, J. N. P., Mott, R. & Flint, J. (2006) Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet 38, 879–887.PubMedCrossRefGoogle Scholar
  128. 128.
    Andersson, L. & Georges, M. (2004) Domestic animal genomics: deciphering the genetics of complex traits. Nat Rev Genet 5, 202–212.PubMedCrossRefGoogle Scholar
  129. 129.
    Carlson, C. S., Eberle, M. A., Kruglyak, L. & Nickerson, D. A. (2004) Mapping complex disease loci in whole-genome association studies. Nature 429, 446–452.PubMedCrossRefGoogle Scholar
  130. 130.
    Smith, J. M. & Haigh, J. (1974) The hitch-hiking effect of a favourable gene. Genet Res 23, 23–35.PubMedCrossRefGoogle Scholar
  131. 131.
    Wright, D., Boije, H., Meadows, J. R. S., Bed’hom, B., Gourichon, D., Vieaud, A., Tixier-Boichard, M., Rubin, C. -J., Imsland, F., Hallböök, F. & Andersson, L. (2009) Transient ectopic expression of SOX5 during embryonic development causes the Pea-comb phenotype in chickens. PloS Genet 5(6), e1000512.PubMedCrossRefGoogle Scholar
  132. 132.
    Meuwissen, T. H., Karlsen, A., Lien, S., Olsaker, I. & Goddard, M. E. (2002) Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping. Genetics 161, 373–379.PubMedGoogle Scholar
  133. 133.
    Riquet, J., Coppieters, W., Cambisano, N., Arranz, J. -J., Berzi, P., Davis, S. K., Grisart, B., Farnir, F. D. R., Karim, L., Mni, M., Simon, P., Taylor, J. F., Vanmanshoven, P., Wagenaar, D., Womack, J. E. & Georges, M. (1999) Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle. Proc Natl Acad Sci USA 96, 9252–9257.PubMedCrossRefGoogle Scholar
  134. 134.
    Goldstein, O., Zangerl, B., Pearce-Kelling, S., Sidjanin, D. J., Kijas, J. W., Felix, J., Acland, G. M. & Aguirre, G. D. (2006) Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome. Genomics 88, 541–550.PubMedCrossRefGoogle Scholar
  135. 135.
    Makinen, H. S., Shikano, T., Cano, J. M. & Merila, J. (2008) Hitchhiking mapping reveals a candidate genomic region for natural selection in three-spined stickleback chromosome VIII. Genetics 178, 453–465.PubMedCrossRefGoogle Scholar
  136. 136.
    Burgess-Herbert, S. L., Cox, A., Tsaih, S.-W. & Paigen, B. (2008) Practical applications of the bioinformatics toolbox for narrowing quantitative trait loci. Genetics 180, 2227–2235.PubMedCrossRefGoogle Scholar
  137. 137.
    Li, R., Lyons, M. A., Wittenburg, H., Paigen, B. & Churchill, G. A. (2005) Combining data from multiple inbred line crosses improves the power and resolution of quantitative trait loci mapping. Genetics 169, 1699–1709.PubMedCrossRefGoogle Scholar
  138. 138.
    Dipetrillo, K., Wang, X., Stylianou, I. M. & Paigen, B. (2005) Bioinformatics toolbox for narrowing rodent quantitative trait loci. Trends Genet 21, 683–691.PubMedCrossRefGoogle Scholar
  139. 139.
    Wang, X. & Paigen, B. (2005) Genetics of variation in HDL cholesterol in humans and mice. Circ Res 96, 27–42.PubMedCrossRefGoogle Scholar
  140. 140.
    Flint, J. & Mackay, T. F. C. (2009) Genetic architecture of quantitative traits in mice, flies, and humans. Genome Res 19, 723–733.PubMedCrossRefGoogle Scholar
  141. 141.
    Yalcin, B., Flint, J. & Mott, R. (2005) Using progenitor strain information to identify quantitative trait nucleotides in outbred mice. Genetics 171, 673–681.PubMedCrossRefGoogle Scholar
  142. 142.
    Legare, M. E., Bartlett, F. S. & Frankel, W. N. (2000) A major effect QTL determined by multiple genes in epileptic el mice. Genome Res 10, 42–48.PubMedGoogle Scholar
  143. 143.
    Lyman, R. F., Lai, C. & Mackay, T. F. (1999) Linkage disequilibrium mapping of molecular polymorphisms at the scabrous locus associated with naturally occurring variation in bristle number in Drosophila melanogaster. Genet Res 74, 303–311.PubMedCrossRefGoogle Scholar
  144. 144.
    Symula, D. J., Frazer, K. A., Ueda, Y., Denefle, P., Stevens, M. E., Wang, Z. E., Locksley, R. & Rubin, E. M. (1999) Functional screening of an asthma QTL in YAC transgenic mice. Nat Genet 23, 241–244.PubMedCrossRefGoogle Scholar
  145. 145.
    Sauer, B. & Henderson, N. (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. PNAS 85, 5166–5170.PubMedCrossRefGoogle Scholar
  146. 146.
    Langenau, D. M., Feng, H., Berghmans, S., Kanki, J. P., Kutok, J. L. & Look, A. T. (2005) Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 102, 6068–6073.PubMedCrossRefGoogle Scholar
  147. 147.
    Aitman, T. J., Glazier, A. M., Wallace, C. A., Cooper, L. D., Norsworthy, P. J., Wahid, F. N., Al-Majali, K. M., Trembling, P. M., Mann, C. J., Shoulders, C. C., Graf, D., St Lezin, E. M., Kurtz, T. W., Kren, V., Pravenec, M., Ibrahimi, A., Abumrad, N. A., Stanton, L. W. & Scott, J. (1999) Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 21, 76–83.PubMedCrossRefGoogle Scholar
  148. 148.
    Gibson, G. & Weir, B. (2005) The quantitative genetics of transcription. Trends Genet 21, 616–623.PubMedCrossRefGoogle Scholar
  149. 149.
    Breitling, R., Li, Y., Tesson, B. M., Fu, J., Wu, C., Wiltshire, T., Gerrits, A., Bystrykh, L. V., de Haan, G., Su, A. I. & Jansen, R. C. (2008) Genetical genomics: spotlight on QTL hotspots. PLoS Genet 4, e1000232.PubMedCrossRefGoogle Scholar
  150. 150.
    Nadeau, J. H. & Frankel, W. N. (2000) The roads from phenotypic variation to gene discovery: mutagenesis versus QTLs. Nat Genet 25, 381–384.PubMedCrossRefGoogle Scholar
  151. 151.
    Sawyer, L. A., Hennessy, J. M., Pexioto, A. A. & Kyriacou, P. (1997) Natural variation in a Drosophila clock gene and temperature compensation. Science 278, 2117–2120.PubMedCrossRefGoogle Scholar
  152. 152.
    Tully, T. (1996) Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives. Proc Natl Acad Sci USA 93, 13460–13467.PubMedCrossRefGoogle Scholar
  153. 153.
    Coates, J. C. & de Bono, M. (2002) Antagonistic pathways in neurons exposed to body fluid regulate social feeding in C. elegans. Nature 419, 925–929.PubMedCrossRefGoogle Scholar
  154. 154.
    de Bono, M., Tobin, D. M., Davis, M. W., Avery, L. & Bargmann, C. I. (2002) Social feeding in C. elegans is induced by neurons that detect aversive stimuli. Nature 419, 899–903.PubMedCrossRefGoogle Scholar
  155. 155.
    de Belle, J. S. & Sokolowksi, M. B. (1989) Genetic localization of foraging (for): a major gene for larval behavior in Drosophila melanogaster. Genetics 123, 157–163.PubMedGoogle Scholar
  156. 156.
    Sokolowski, M. B. (1998) Genes for normal behavioural variation: recent clues from flies and worms. Neuron 21, 463–466.PubMedCrossRefGoogle Scholar
  157. 157.
    Driever, W. & Al, E. (1996) A genetic screen for mutations affecting embryogenesis in the zebrafish. Development 123, 37–46.PubMedGoogle Scholar
  158. 158.
    Haffter, P. (1996) The identification of genes with unique and essential function in the development of the zebrafish, Danio rerio. Development 123, 1–36.PubMedGoogle Scholar
  159. 159.
    Walker, C. & Streisinger, G. (1983) Induction of mutations by gamma-ras in pregonial germ cells of zebrafish embryos. Genetics 103, 125–136.PubMedGoogle Scholar
  160. 160.
    Amsterdam, A. & Hopkins, N. (2006) Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. Trends Genet 22, 473–478.PubMedCrossRefGoogle Scholar
  161. 161.
    Darland, T. & Dowling, J. E. (2001) Behavioral screening for cocaine sensitivity in mutagenized zebrafish. Proc Natl Acad Sci USA 98, 11691–11696.PubMedCrossRefGoogle Scholar
  162. 162.
    Baier, H. (2000) Zebrafish on the move: towards a behavior-genetic analysis of vertebrate vision. Curr Neurobiol 10, 451–455.CrossRefGoogle Scholar
  163. 163.
    Neuhass, S. C. (1999) Genetic disorders of vision revealed by a behavioural screen of 400 essential loci in zebrafish. J Neurosci 19, 8603–8615.Google Scholar
  164. 164.
    Granato, M. (1996) Genes controlling and mediating locomotion behaviour of the zebrafish embryo and larvae. Development 123, 399–413.PubMedGoogle Scholar
  165. 165.
    Lorent, K. (2001) The zebrafish space cadet gene controls axonal pathfinding of neurons that modulate fast turning movements. Development 128, 2131–2142.PubMedGoogle Scholar
  166. 166.
    Baraban, S. C., Dinday, M. T., Castro, P. A., Chege, S., Guyenet, S. & Taylor, M. R. (2007) A large-scale mutagenesis screen to identify seizure-resistant zebrafish. Epilepsia 48, 1151–1157.PubMedCrossRefGoogle Scholar
  167. 167.
    Henderson, N. D., Turri, M. G., Defries, J. C. & Flint, J. (2004) QTL analysis of multiple behavioral measures of anxiety in mice. Behav Genet 34, 267–293.PubMedCrossRefGoogle Scholar
  168. 168.
    Wright, D., Nakamichi, R., Krause, J. & Butlin, R. K. (2006c) QTL analysis of behavioural and morphological differentiation between wild and laboratory zebrafish (Danio rerio). Behav Genet 36, 271–284.PubMedCrossRefGoogle Scholar
  169. 169.
    Croft, D. P., Krause, J. & James, R. (2004) Social networks in the guppy (Poecilia reticulata). Proc R Soc Lond Biol Lett 271, 516–519.CrossRefGoogle Scholar
  170. 170.
    Nakamichi, R., Ukai, Y. & Kishino, H. (2001) Detection of closely linked multiplre quantitative trait loci using a genetic algorithm. Genetics 158, 463–475.PubMedGoogle Scholar
  171. 171.
    Carlborg, O. & Andersson, L. (2002) Use of randomization testing to detect multiple epistatic QTLs. Genet Res 79, 175–184.PubMedCrossRefGoogle Scholar
  172. 172.
    Carlborg, O., Andersson, L. & Kinghorn, B. (2000) The use of a genetic algorithm for simultaneous mapping of multiple interacting quantitative trait loci. Genetics 155, 2003–2010.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Dominic Wright
    • 1
  1. 1.IFM-BiologyLinköping UniversityLinköpingSweden

Personalised recommendations