High-resolution genetic maps are required for mapping complex traits and for the study of recombination. We report the highest density genetic map yet created for any organism, except humans. Using more than 10,000 single nucleotide polymorphisms evenly spaced across the mouse genome, we have constructed genetic maps for both outbred and inbred mice, and separately for males and females. Recombination rates are highly correlated in outbred and inbred mice, but show relatively low correlation between males and females. Differences between male and female recombination maps and the sequence features associated with recombination are strikingly similar to those observed in humans. Genetic maps are available from http://gscan.well.ox.ac.uk/#genetic_map and as supporting information to this publication.
References
[1]
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, et al. (1996) A comprehensive genetic map of the mouse genome. Nature 380: 149–152.
[2]
European Backcross Collaborative Group (1994) Towards high resolution maps of the mouse and human genomes—a facility for ordering markers to 0.1 cM resolution. Hum Mol Genet 3: 621–627.
[3]
Rhodes M, Straw R, Fernando S, Evans A, Lacey T, et al. (1998) A high-resolution microsatellite map of the mouse genome. Genome Res 8: 531–542.
[4]
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: 520–562.
[5]
Lindblad-Toh K, Winchester E, Daly MJ, Wang DG, Hirschhorn JN, et al. (2000) Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse. Nat Genet 24: 381–386.
[6]
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: 3380–3385.
[7]
Pletcher MT, McClurg P, Batalov S, Su AI, Barnes SW, et al. (2004) Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse. PLoS Biol 2: e393.. DOI: 10.1371/journal.pbio.0020393.
[8]
Moran JL, Bolton AD, Tran PV, Brown A, Dwyer ND, et al. (2006) Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse. Genome Res 16: 436–440.
[9]
Crawford DC, Bhangale T, Li N, Hellenthal G, Rieder MJ, et al. (2004) Evidence for substantial fine-scale variation in recombination rates across the human genome. Nat Genet 36: 700–706.
[10]
McVean GA, Myers SR, Hunt S, Deloukas P, Bentley DR, et al. (2004) The fine-scale structure of recombination rate variation in the human genome. Science 304: 581–584.
[11]
Valdar W, Solberg LC, Gauguier D, Burnett S, Klenerman P, et al. (2006) Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet 38: 879–887.
[12]
Talbot CJ, Nicod A, Cherny SS, Fulker DW, Collins AC, et al. (1999) High-resolution mapping of quantitative trait loci in outbred mice. Nat Genet 21: 305–308.
[13]
Darvasi A, Soller M (1995) Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141: 1199–1207.
[14]
Daw EW, Thompson EA, Wijsman EM (2000) Bias in multipoint linkage analysis arising from map misspecification. Genet Epidemiol 19: 366–380.
[15]
Fingerlin TE, Abecasis GR, Boehnke M (2006) Using sex-averaged genetic maps in multipoint linkage analysis when identity-by-descent status is incompletely known. Genet Epidemiol 30: 384–396.
[16]
Myers S, Bottolo L, Freeman C, McVean G, Donnelly P (2005) A fine-scale map of recombination rates and hotspots across the human genome. Science 310: 321–324.
[17]
Winckler W, Myers SR, Richter DJ, Onofrio RC, McDonald GJ, et al. (2005) Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308: 107–111.
[18]
Demarest K, Koyner J, McCaughran J Jr., Cipp L, Hitzemann R (2001) Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity. Behav Genet 31: 79–91.
[19]
Cervino AC, Li G, Edwards S, Zhu J, Laurie C, et al. (2005) Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels. Genomics 86: 505–517.
[20]
Lander ES, Green P (1987) Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A 84: 2363–2367.
[21]
Broman KW, Wu H, Sen S, Churchill GA (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19: 889–890.
[22]
Sampson SB, Higgins DC, Elliot RW, Taylor BA, Lueders KK, et al. (1998) An edited linkage map for the AXB and BXA recombinant inbred mouse strains. Mamm Genome 9: 688–694.
[23]
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 Biol 2: 1–0046. 18. research0046.
[24]
Taylor BA (1978) Recombinant inbred strains: Use in gene mapping. In: Morse HC III, editor. Origins of inbred mice: Proceedings of a workshop, Bethesda, Maryland, February 14–16, 1978. New York: Academic Press. pp. 423–438.
[25]
Taylor BA, Wnek C, Kotlus BS, Roemer N, MacTaggart T, et al. (1999) Genotyping new BXD recombinant inbred mouse strains and comparison of BXD and consensus maps. Mamm Genome 10: 335–348.
[26]
Peirce JL, Lu L, Gu J, Silver LM, Williams RW (2004) A new set of BXD recombinant inbred lines from advanced intercross populations in mice. BMC Genet 5: 7.
[27]
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, et al. (2002) The structure of haplotype blocks in the human genome. Science 296: 2225–2229.
[28]
Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, et al. (2005) Evidence of a large-scale functional organization of mammalian chromosomes. PLoS Genet 1: e33.. DOI: 10.1371/journal.pgen.0010033.
[29]
Laurie DA, Hulten MA (1985) Further studies on chiasma distribution and interference in the human male. Ann Hum Genet 49 (Pt 3): 203–214.
[30]
Pardo-Manuel de Villena F, Sapienza C (2001) Recombination is proportional to the number of chromosome arms in mammals. Mamm Genome 12: 318–322.
[31]
Jensen-Seaman MI, Furey TS, Payseur BA, Lu Y, Roskin KM, et al. (2004) Comparative recombination rates in the rat, mouse, and human genomes. Genome Res 14: 528–538.
[32]
Broman KW, Murray JC, Sheffield VC, White RL, Weber JL (1998) Comprehensive human genetic maps: Individual and sex-specific variation in recombination. Am J Hum Genet 63: 861–869.
[33]
Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, et al. (2002) A high-resolution recombination map of the human genome. Nat Genet 31: 241–247.
[34]
Lynn A, Schrump S, Cherry J, Hassold T, Hunt P (2005) Sex, not genotype, determines recombination levels in mice. Am J Hum Genet 77: 670–675.
[35]
Petkov PM, Cassell MA, Sargent EE, Donnelly CJ, Robinson P, et al. (2004) Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83: 902–911.
[36]
Wigginton JE, Abecasis GR (2005) PEDSTATS: Descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics 21: 3445–3447.
[37]
O'Connell JR, Weeks DE (1998) PedCheck: A program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63: 259–266.
[38]
Kosambi DD (1944) The estimation of map distances from recombination values. Ann Eugen 12: 172–175.
[39]
Lincoln SE, Lander ES (1992) Systematic detection of errors in genetic linkage data. Genomics 14: 604–610.
[40]
Potter SC, Clarke L, Curwen V, Keenan S, Mongin E, et al. (2004) The Ensembl analysis pipeline. Genome Res 14: 934–941.
[41]
Taylor MS, Kai C, Kawai J, Carninci P, Hayashizaki Y, et al. (2006) Heterotachy in mammalian promoter evolution. PLoS Genet 2: e30.. DOI: 10.1371/journal.pgen.0020030.
