• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Apr 2002; 160(4): 1609–1618.
PMCID: PMC1462050

Simultaneous detection and fine mapping of quantitative trait loci in mice using heterogeneous stocks.


We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived from known founder strains. The experimental design is an F(2) cross between the HS and a genetically distinct line, such as one carrying a knockout or transgene. QTL detection is performed by a standard genome scan with approximately 100 markers and fine mapping by typing the same animals using densely spaced markers over those candidate regions detected by the scan. The analysis uses an extension of the dynamic-programming technique employed previously to fine map QTL in HS mice. We show by simulation that a QTL accounting for 5% of the total variance can be detected and fine mapped with >50% probability to within 3 cM by genotyping approximately 1500 animals.

Full Text

The Full Text of this article is available as a PDF (126K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Darvasi A, Soller M. Advanced intercross lines, an experimental population for fine genetic mapping. Genetics. 1995 Nov;141(3):1199–1207. [PMC free article] [PubMed]
  • Flint J, Mott R. Finding the molecular basis of quantitative traits: successes and pitfalls. Nat Rev Genet. 2001 Jun;2(6):437–445. [PubMed]
  • Long AD, Mullaney SL, Mackay TF, Langley CH. Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. Genetics. 1996 Dec;144(4):1497–1510. [PMC free article] [PubMed]
  • McPeek MS. From mouse to human: fine mapping of quantitative trait loci in a model organism. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12389–12390. [PMC free article] [PubMed]
  • Mott R, Talbot CJ, Turri MG, Collins AC, Flint J. A method for fine mapping quantitative trait loci in outbred animal stocks. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12649–12654. [PMC free article] [PubMed]
  • Ramírez-Solis R, Liu P, Bradley A. Chromosome engineering in mice. Nature. 1995 Dec 14;378(6558):720–724. [PubMed]
  • Abney M, McPeek MS, Ober C. Estimation of variance components of quantitative traits in inbred populations. Am J Hum Genet. 2000 Feb;66(2):629–650. [PMC free article] [PubMed]
  • Talbot CJ, Nicod A, Cherny SS, Fulker DW, Collins AC, Flint J. High-resolution mapping of quantitative trait loci in outbred mice. Nat Genet. 1999 Mar;21(3):305–308. [PubMed]
  • Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, Al-Majali KM, Trembling PM, Mann CJ, Shoulders CC, et al. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet. 1999 Jan;21(1):76–83. [PubMed]
  • Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science. 1995 Jul 14;269(5221):230–234. [PubMed]
  • Alpert KB, Tanksley SD. High-resolution mapping and isolation of a yeast artificial chromosome contig containing fw2.2: a major fruit weight quantitative trait locus in tomato. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15503–15507. [PMC free article] [PubMed]
  • Wells C, Brown SD. Genomics meets genetics: towards a mutant map of the mouse. Mamm Genome. 2000 Jul;11(7):472–477. [PubMed]
  • Xu S, Yi N. Mixed model analysis of quantitative trait loci. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14542–14547. [PMC free article] [PubMed]
  • Darvasi A. Interval-specific congenic strains (ISCS): an experimental design for mapping a QTL into a 1-centimorgan interval. Mamm Genome. 1997 Mar;8(3):163–167. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...