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Gene Mapping

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Genetics of the Mouse


Now that the sequence of the mouse genome is completely known, the position of any gene of the species can be accurately and rapidly established by searching the appropriate database. In this context, a chapter devoted to gene mapping and genetic maps might appear somewhat outdated, not to say useless. However, we thought that it might be interesting to reconsider this subject for at least three reasons. The first is that gene mapping has been a major component of the activities of mouse geneticists during most of the twentieth century; it is then interesting, if only from a historical point of view, to briefly describe the techniques and methods that have made the genetic map of the mouse the richest and most documented map of all mammals, including humans, for nearly 50 years. The second reason is more fundamental and refers to the many mutations that occur spontaneously in the breeding nuclei of inbred strains or those that are induced by mutagenic agents. All these mutations are initially characterized by an abnormal phenotype and some of them may appear of potential interest, for example, as models of human diseases. However, annotating and characterizing all these mutations requires that they be first carefully located on a chromosome and analyzed at the molecular level, when relevant.

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  1. 1.

    The structure of the mitochondrial genome (or mtDNA) is discussed in Chap. 5; here we consider only the genes in the nuclear genome.

  2. 2.

    In this type of cross, the classical recessive allele Tyr c (albino) cannot be used because it has an epistatic interaction with pink-eyed dilution, affecting eye and coat color, which makes phenotyping difficult.

  3. 3.

    +/d? indicates that the actual genotype of the mouse is not known. It may be either +/+ or +/d.

  4. 4.

    Reading the original publications is sometimes difficult due to the use of a nomenclature system different from the one in use nowadays. The dilute locus, for example, was designated “density” with two alleles: D and d. Nowadays, the same gene is symbolized Myo5a d.

  5. 5.

    A review by Dr. Eva Eicher from The Jackson Laboratory is a rich source of information concerning the historical aspects of mouse gene mapping and the progressive development of the genetic map in this species (Eicher 1981).

  6. 6.

    It is now established that there are very few genes on the Y chromosome.

  7. 7.

    The presumption that the twenty LGs identified at that time were each located on different chromosomes was shown to be wrong. In fact, a few genes were still mis-assigned and one LG was not yet identified.

  8. 8.

    If the alleles at the A and B locus were not linked or if the linkage was not known, the symbols for the genotypes would be: A/A; b/b for the male and a/a; B/B for the female.

  9. 9.

    When one of the mutant alleles (M) is dominant over wild type (+): the phase is +M/am for coupling and aM/+m for repulsion. In other words, the dominant alleles are associated on the same chromosome when in coupling.

  10. 10.

    Many of these software programs are listed at: The most popular are MAPMAKER, MAPMANAGER and GENE LINK.

  11. 11.

    When the computed genetic distances are short or very short (<3 cM), it is recommended to express them with the lower and upper limits of the exact 95 % confidence interval calculated from the binomial distribution, as they appear in Table D5 and D6 (pp. 303–304) of Silver’s book Mouse Genetics: concepts and application, Oxford University, 1995. This textbook is freely available at the Mouse Genome Informatics website.

  12. 12.

    The physical (or DNA) size of the genome is estimated to be 2.7 Gb, and the mouse genetic (meiotic) map is estimated to span ~1,600 cM.

  13. 13.

    This equivalence between cM and kb/Mb applies to the mouse only. In the human species, 1 cM is equivalent to ~0.7–1 Mb of DNA.

  14. 14.

  15. 15.

    Preparing a four-point backcross involving traditional or classical genetic markers, i.e., those that are scored by scrutinizing the mice one after the other, requires a lot of crosses because the markers in question are almost always in independent stocks or strains and first have to be gathered in the same stock by sexual reproduction.

  16. 16.

    Most of the genes used for mapping in the past are now cloned and their DNA sequence is known. For LG I, for example, Tyr is the gene encoding tyrosinase and Oca2 (oculocutaneous albinism II) is a gene encoding a transmembrane transporter essential for normal pigmentation. Both genes are involved in the production of melanin, and both are cloned and sequenced. The two genes can then be considered under two aspects: either as a mouse with a specific coat color, or as fluorescent dots on a mouse chromosome (see Chap. 3). In this particular case, it is chromosome 7 (bearing the whole of LG I).

  17. 17.

    The breakpoint of the reciprocal translocation T(2;8)26H on chromosome 2 is within the Agouti locus and inactivates this gene. Mice homozygous for the translocation, which are easy to identify by analysis of the karyotype, are also non-agouti (with a black coat color). This observation (and others) allowed it to be established that LG V (including the Agouti locus) was on Chr 2.

  18. 18.

    Accumulation of these new mutant alleles was, in part, a direct consequence of the use of the mouse as a model organism for the evaluation of the effects of radiation or of chemical mutagens on the genome, and an indirect consequence of inbreeding as a mating system. Inbreeding has no effect on the mutation rate, but it increases the chance that individuals will be homozygous for recessive mutations, which, accordingly, are more easily identifiable.

  19. 19.

    During the years 1965–1975, when the genetic map of the mouse was expanding, researchers at Harwell MRC and The Jackson Laboratory were using the so-called linkage testing (or linkage tester) stocks. These stocks were homozygous for up to seven carefully selected recessive, fully viable, and fully penetrant coat color markers mapping to different chromosomes. The phenotype of each of these markers could be detected independently, with no interference from the other markers. One of these stocks was the famous PT stock, which was extensively used at Oak Ridge by W.L. & L.B. Russell for estimating the rate of induced mutations either with chemicals or radiation. The PT stock was homozygous for seven markers on five chromosomes: a/a; b/b; c ch-p/c ch-p; d-se/d-se; wa1/wa1.

  20. 20.

    Repeated units such as T, CA, CT, and CAG are among the most common.

  21. 21.

    In fact, the microsatellites are more mutable than most other molecular markers previously described, but their mutation, in general, generates a novel allele that is not identical to any of the parental alleles. In these conditions the structural instability does not result in a confusion. It may, however, be a problem when microsatellites are used for the genetic monitoring of inbred strains (see Chap. 9).

  22. 22.

    Around 70 % of SSLPs (microsatellites) or SNPs have been found to be polymorphic between any two strains derived from progenitors of independent (wild) origins of the same Mus genus. Altogether, this means that around 30,000 SNPs or SSLPs could (potentially) be used for the purpose of mapping in a cross involving two inbred strains derived from two different subspecies.

  23. 23.

    A bin is a group of syntenic genetic markers that have not been separated (ordered) by meiotic recombination in a given cross.

  24. 24.

    The mapping of these microsatellites has been achieved in two successive steps. First, all the 982 DNA samples of the backcross progeny were initially typed for 78 primary anchor loci spanning the entire genome, with 3–6 anchors per chromosome. In a second step, only the DNA samples demonstrated to be recombinant in one or the other of these intervals tagged by the 78 primary anchor loci were typed for the greatest possible number of markers located (or presumed to be located) in these regions.

  25. 25.

    In fact, and as we shall see in Chap. 5, the mouse genome has been sequenced by using a global strategy known as whole-genome sequencing or WGS. However, the physical map of the mouse genome, established by anchoring a variety of DNA clones on the genetic map, has been helpful in many experiments of positional cloning, and is still used for the analysis of quantitative traits.

  26. 26.

    This is sometimes referred to as a “magnifying glass effect.”.

  27. 27.

    Reverse genetics is the opposite approach: its aim is to characterize the function of a gene by analyzing the consequences at the phenotypic level of alterations occurring spontaneously or engineered by researchers at the DNA level.

  28. 28.

    5–6 markers for the largest chromosomes, 4–5 for the medium-sized and 3 for the smallest is ideal.

  29. 29.

    The first sample of 50–60 mutant mice generally consists of the first offspring of the larger population.

  30. 30.

    This is why it is best to perform genotyping as early as possible, before weaning.

  31. 31.

    As we will explain in the next chapter, gene density is extremely variable from one genomic region to the next. Accordingly, these estimations must be considered only as indications.

  32. 32.

    Because there is contiguity in their sequence.


  • Bailey DW (1971) Recombinant-inbred strains. An aid to finding identity, linkage, and function of histocompatibility and other genes. Transplantation 11:325–327

    Article  CAS  PubMed  Google Scholar 

  • Bateson W, Punnett RC (1906) Comb characters. Rep Evol Comm R Soc Lond II:11–16

    Google Scholar 

  • Bonhomme F, Selander RK (1978) Estimating total genic diversity in the house mouse. Biochem Genet 16:287–297

    Article  CAS  PubMed  Google Scholar 

  • Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331

    Google Scholar 

  • Burgio G, Baylac M, Heyer E, Montagutelli X (2012) Nasal bone shape is under complex epistatic genetic control in mouse interspecific recombinant congenic strains. PLoS One 7:e37721. Epub 2012 May 25

    Google Scholar 

  • Burgio G, Szatanik M, Guénet JL, Arnau MR, Panthier JJ, Montagutelli X (2007) Interspecific recombinant congenic strains between C57BL/6 and mice of the Mus spretus species: a powerful tool to dissect genetic control of complex traits. Genetics 177:2321–2333

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cox DR, Burmeister M, Price ER, Kim S, Myers RM (1990) Radiation hybrid mapping: a somatic cell genetic method for constructing high resolution maps of mammalian chromosomes. Science 250:245–250

    Article  CAS  PubMed  Google Scholar 

  • Cuénot L (1902) La loi de Mendel et l’hérédité de la pigmentation chez les souris. Arch Zool exp gén 3e séries 3:xxvii–xxx

    Google Scholar 

  • Darbishire AD (1904) On the result of crossing Japanese waltzing with albino mice. Biometrika 3:1–51

    Article  Google Scholar 

  • Davisson MT, Akeson EC (1993) Recombination suppression by heterozygous Robertsonian chromosomes in the mouse. Genetics 133:649–667

    CAS  PubMed Central  PubMed  Google Scholar 

  • Davisson MT, Eicher EM, Green MC (1976) Genes on chromosome 3 of the mouse. J Hered 67:155–156

    CAS  PubMed  Google Scholar 

  • Demant P (2003) Cancer susceptibility in the mouse: genetics, biology and implications for human cancer. Nat Rev Genet 4:721–734

    Article  CAS  PubMed  Google Scholar 

  • Demant P, Hart AA (1986) Recombinant congenic strains–a new tool for analyzing genetic traits determined by more than one gene. Immunogenetics 24:416–422

    Article  CAS  PubMed  Google Scholar 

  • Dietrich WF, Miller JC, Steen RG, Merchant M, Damron D, Nahf R, Gross A, Joyce DC, Wessel M, Dredge RD, Andre Marquis A, Stein LD, Goodman N, Page DC, Lander E (1994) A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nat Genet 2:220–245

    Article  Google Scholar 

  • Eicher EM (1971) The identification of the chromosome bearing linkage group XII in the mouse. Genetics 69:267–271

    CAS  PubMed Central  PubMed  Google Scholar 

  • Eicher EM (1978) Murine ovarian teratomas and parthenotes as cytogenetic tools. Cytogenet Cell Genet 20:232–239

    Article  CAS  PubMed  Google Scholar 

  • Eicher EM (1981) Foundation for the future: formal genetics of the mouse. In: Mammalian genetics and cancer: the Jackson laboratory fiftieth anniversary symposium. Alan R. Liss, Inc New York, p 7–49

    Google Scholar 

  • Eicher EM, Washburn LL (1978) Assignment of genes to regions of mouse chromosomes. Proc Natl Acad Sci USA 75:946–950

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandez-Gonzalez A, La Spada AR, Treadaway J, Higdon JC, Harris BS, Sidman RL, Morgan JI, Zuo J (2002) Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1. Science 295:1904–1906

    Article  CAS  PubMed  Google Scholar 

  • Flaherty L, Herron B (1998) The new kid on the block—a whole genome mouse radiation hybrid panel. Mamm Genome 9:417–418

    Article  CAS  PubMed  Google Scholar 

  • Gates WH (1927) Linkage of Short Ear and Density in the House Mouse. Proc Natl Acad Sci USA 13:575–578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gregory SG, Sekhon M, Schein J, Zhao S, Osoegawa K, Scott CE, Evans RS, Burridge PW, Cox TV, Fox CA, Hutton RD, Mullenger IR, Phillips KJ, Smith J, Stalker J, Threadgold GJ, Birney E, Wylie K, Chinwalla A, Wallis J, Hillier L, Carter J, Gaige T, Jaeger S, Kremitzki C, Layman D, Maas J, McGrane R, Mead K, Walker R, Jones S, Smith M, Asano J, Bosdet I, Chan S, Chittaranjan S, Chiu R, Fjell C, Fuhrmann D, Girn N, Gray C, Guin R, Hsiao L, Krzywinski M, Kutsche R, Lee SS, Mathewson C, McLeavy C, Messervier S, Ness S, Pandoh P, Prabhu AL, Saeedi P, Smailus D, Spence L, Stott J, Taylor S, Terpstra W, Tsai M, Vardy J, Wye N, Yang G, Shatsman S, Ayodeji B, Geer K, Tsegaye G, Shvartsbeyn A, Gebregeorgis E, Krol M, Russell D, Overton L, Malek JA, Holmes M, Heaney M, Shetty J, Feldblyum T, Nierman WC, Catanese JJ, Hubbard T, Waterston RH, Rogers J, de Jong PJ, Fraser CM, Marra M, McPherson JD, Bentley DR (2002) A physical map of the mouse genome. Nature 418:743–750

    Article  CAS  PubMed  Google Scholar 

  • Grüneberg H (1935) A three-factor linkage experiment in the mouse. J Genet XXXI:157–162

    Google Scholar 

  • Haldane JBS, Sprunt AD, Haldane NM (1915) Reduplication in mice. J Genet 5:133–135

    Article  Google Scholar 

  • Hearne CM, McAleer MA, Love JM, Aitman TJ, Cornall RJ, Ghosh S, Knight AM, Prins JB, Todd JA (1991) Additional microsatellite markers for mouse genome mapping. Mamm Genome 1:273–282

    Article  CAS  PubMed  Google Scholar 

  • Hudson TJ, Church DM, Greenaway S, Nguyen H, Cook A, Steen RG, Van Etten WJ, Castle AB, Strivens MA, Trickett P, Heuston C, Davison C, Southwell A, Hardisty R, Varela-Carver A, Haynes AR, Rodriguez-Tome P, Doi H, Ko MS, Pontius J, Schriml L, Wagner L, Maglott D, Brown SD, Lander ES, Schuler G, Denny P (2001) A radiation hybrid map of mouse genes. Nat Genet 29:201–205

    Google Scholar 

  • Koseki H, Zachgo J, Mizutani Y, Simon-Chazottes D, Guénet JL, Balling R, Gossler A (1993) Fine genetic mapping of the proximal part of mouse chromosome 2 excludes Pax-8 as a candidate gene for Danforth’s short tail (Sd). Mamm Genome 4:324–327

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14(5–6):143–149

    Article  CAS  PubMed  Google Scholar 

  • Lord EM, Gates WH (1929) Shaker, a new mutation of the house mouse (Mus musculus). Am Nat 63:435–442

    Google Scholar 

  • Love JM, Knight AM, McAleer MA, Todd JA (1990) Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res 18:4123–4130

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lyon MF (1969) Mapping data. Mouse News Lett 40:26

    Google Scholar 

  • Mashimo T, Glaser P, Lucas M, Simon-Chazottes D, Ceccaldi PE, Montagutelli X, Desprès P, Guénet JL (2003) Structural and functional genomics and evolutionary relationships in the cluster of genes encoding murine 2′,5′-oligoadenylate synthetases. Genomics 82:537–552

    Article  CAS  PubMed  Google Scholar 

  • Mashimo T, Hadjebi O, Amair-Pinedo F, Tsurumi T, Langa F, Serikawa T, Sotelo C, Guénet JL, Rosa JL (2009) Progressive Purkinje cell degeneration in tambaleante mutant mice is a consequence of a missense mutation in HERC1 E3 ubiquitin ligase. PLoS Genet 5(12):e1000784

    Article  PubMed Central  PubMed  Google Scholar 

  • McCarthy LC, Terrett J, Davis ME, Knights CJ, Smith AL et al (1997) A first-generation whole genome-radiation hybrid map spanning the mouse genome. Genome Res 7:1153–1161

    CAS  PubMed Central  PubMed  Google Scholar 

  • Minty AJ, Alonso S, Guénet JL, Buckingham ME (1983) Number and organization of actin-related sequences in the mouse genome. J Mol Biol 167:77–101

    Article  CAS  PubMed  Google Scholar 

  • Montagutelli X, Serikawa T, Guénet JL (1991) PCR-analyzed microsatellites: data concerning laboratory and wild-derived mouse inbred strains. Mamm Genome 1:255–259

    Article  CAS  PubMed  Google Scholar 

  • Nijman IJ, Kuipers S, Verheul M, Guryev V, Cuppen E (2008) A genome-wide SNP panel for mapping and association studies in the rat. BMC Genom 9:95

    Article  Google Scholar 

  • Osoegawa K, Tateno M, Woon PY, Frengen E, Mammoser AG, Catanese JJ, Hayashizaki Y, de Jong PJ (2000) Bacterial artificial chromosome libraries for mouse sequencing and functional analysis. Genome Res 1:116–128

    Google Scholar 

  • Paigen K, Petkov P (2010) Mammalian recombination hot spots: properties, control and evolution. Nat Rev Genet 11:221–233

    Article  CAS  PubMed  Google Scholar 

  • Petkov PM, Cassell MA, Sargent EE, Donnelly CJ, Robinson P, Crew V, Asquith S, Haar RV, Wiles MV (2004a) Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902–911

    Article  CAS  PubMed  Google Scholar 

  • Petkov PM, Ding Y, Cassell MA, Zhang W, Wagner G, Sargent EE, Asquith S, Crew V, Johnson KA, Robinson P, Scott VE, Wiles MV (2004b) An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res 14(9):1806–1811

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Petkov PM, Broman KW, Szatkiewicz JP, Paigen K (2007) Crossover interference underlies sex differences in recombination rates. Trends Genet 23:539–542

    Article  CAS  PubMed  Google Scholar 

  • Pontecorvo G (1976) Polyethylene glycol (PEG) in the production of mammalian somatic cell hybrids. Cytogenet Cell Genet 16:399–400

    Article  CAS  PubMed  Google Scholar 

  • Rhodes M, Straw R, Fernando S, Evans A, Lacey T, Dearlove A, Greystrong J, Walker J, Watson P, Weston P, Kelly M, Taylor D, Gibson K, Mundy C, Bourgade F, Poirier C, Simon D, Brunialti AL, Montagutelli X, Guénet JL, Haynes A, Brown SD (1998) A high-resolution microsatellite map of the mouse genome. Genome Res 8:531–542

    CAS  PubMed  Google Scholar 

  • Serikawa T, Montagutelli X, Simon-Chazottes D, Guénet JL (1992) Polymorphisms revealed by PCR with single, short-sized, arbitrary primers are reliable markers for mouse and rat gene mapping. Mamm Genome 3:65–72

    Article  CAS  PubMed  Google Scholar 

  • Silver J (1985) Confidence limits for estimates of gene linkage based on analysis of recombinant inbred strains. J Hered 76:436–440

    CAS  PubMed  Google Scholar 

  • Silver J, Buckler CE (1986) Statistical considerations for linkage analysis using recombinant inbred strains and backcrosses. Proc Natl Acad Sci USA 83:1423–1427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Silver LM (1995) Mouse genetics—concepts and applications. Oxford University Press, Oxford

    Google Scholar 

  • Taylor BA (1978) Recombinant inbred strains: use in gene mapping. In: Morse HC III (ed) Origins of inbred mice. Academic Press, NY, pp 423–438

    Chapter  Google Scholar 

  • 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(11):RESEARCH0046. Epub 2001 Oct 22

    Google Scholar 

  • Yang H, Ding Y, Hutchins LN, Szatkiewicz J, Bell TA, Paigen BJ, Graber JH, de Villena FP, Churchill GA (2009) A customized and versatile high-density genotyping array for the mouse. Nat Methods 6(9):663–666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yokoyama T, Silversides DW, Waymire KG, Kwon BS, Takeuchi T, Overbeek PA (1990) Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice. Nucleic Acids Res 18(24):7293–7298

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    Article  CAS  PubMed  Google Scholar 

  • Zou F, Gelfond JA, Airey DC, Lu L, Manly KF, Williams RW, Threadgill DW (2005) Quantitative trait locus analysis using recombinant inbred intercrosses: theoretical and empirical considerations. Genetics 170(3):1299–1311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Guenet, JL., Benavides, F., Panthier, JJ., Montagutelli, X. (2015). Gene Mapping. In: Genetics of the Mouse. Springer, Berlin, Heidelberg.

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