Skip to main content
Genetics logoLink to Genetics
. 1999 Jan;151(1):373–386. doi: 10.1093/genetics/151.1.373

Statistical methods for mapping quantitative trait loci from a dense set of markers.

J Dupuis 1, D Siegmund 1
PMCID: PMC1460471  PMID: 9872974

Abstract

Lander and Botstein introduced statistical methods for searching an entire genome for quantitative trait loci (QTL) in experimental organisms, with emphasis on a backcross design and QTL having only additive effects. We extend their results to intercross and other designs, and we compare the power of the resulting test as a function of the magnitude of the additive and dominance effects, the sample size and intermarker distances. We also compare three methods for constructing confidence regions for a QTL: likelihood regions, Bayesian credible sets, and support regions. We show that with an appropriate evaluation of the coverage probability a support region is approximately a confidence region, and we provide a theroretical explanation of the empirical observation that the size of the support region is proportional to the sample size, not the square root of the sample size, as one might expect from standard statistical theory.

Full Text

The Full Text of this article is available as a PDF (199.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson L., Haley C. S., Ellegren H., Knott S. A., Johansson M., Andersson K., Andersson-Eklund L., Edfors-Lilja I., Fredholm M., Hansson I. Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science. 1994 Mar 25;263(5154):1771–1774. doi: 10.1126/science.8134840. [DOI] [PubMed] [Google Scholar]
  2. Bayés M., Valverde D., Balcells S., Grinberg D., Vilageliu L., Benítez J., Ayuso C., Beneyto M., Baiget M., Gonzàlez-Duarte R. Evidence against involvement of recoverin in autosomal recessive retinitis pigmentosa in 42 Spanish families. Hum Genet. 1995 Jul;96(1):89–94. doi: 10.1007/BF00214192. [DOI] [PubMed] [Google Scholar]
  3. Churchill G. A., Doerge R. W. Empirical threshold values for quantitative trait mapping. Genetics. 1994 Nov;138(3):963–971. doi: 10.1093/genetics/138.3.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conneally P. M., Edwards J. H., Kidd K. K., Lalouel J. M., Morton N. E., Ott J., White R. Report of the Committee on Methods of Linkage Analysis and Reporting. Cytogenet Cell Genet. 1985;40(1-4):356–359. doi: 10.1159/000132186. [DOI] [PubMed] [Google Scholar]
  5. Darvasi A., Weinreb A., Minke V., Weller J. I., Soller M. Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. Genetics. 1993 Jul;134(3):943–951. doi: 10.1093/genetics/134.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dupuis J., Brown P. O., Siegmund D. Statistical methods for linkage analysis of complex traits from high-resolution maps of identity by descent. Genetics. 1995 Jun;140(2):843–856. doi: 10.1093/genetics/140.2.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feingold E., Brown P. O., Siegmund D. Gaussian models for genetic linkage analysis using complete high-resolution maps of identity by descent. Am J Hum Genet. 1993 Jul;53(1):234–251. [PMC free article] [PubMed] [Google Scholar]
  8. Haley C. S., Knott S. A. A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity (Edinb) 1992 Oct;69(4):315–324. doi: 10.1038/hdy.1992.131. [DOI] [PubMed] [Google Scholar]
  9. Jacob H. J., Lindpaintner K., Lincoln S. E., Kusumi K., Bunker R. K., Mao Y. P., Ganten D., Dzau V. J., Lander E. S. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell. 1991 Oct 4;67(1):213–224. doi: 10.1016/0092-8674(91)90584-l. [DOI] [PubMed] [Google Scholar]
  10. Jansen R. C. Controlling the type I and type II errors in mapping quantitative trait loci. Genetics. 1994 Nov;138(3):871–881. doi: 10.1093/genetics/138.3.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Korol A. B., Ronin Y. I., Kirzhner V. M. Interval mapping of quantitative trait loci employing correlated trait complexes. Genetics. 1995 Jul;140(3):1137–1147. doi: 10.1093/genetics/140.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kruglyak L., Lander E. S. High-resolution genetic mapping of complex traits. Am J Hum Genet. 1995 May;56(5):1212–1223. [PMC free article] [PubMed] [Google Scholar]
  13. Lander E. S., Botstein D. Mapping complex genetic traits in humans: new methods using a complete RFLP linkage map. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):49–62. doi: 10.1101/sqb.1986.051.01.007. [DOI] [PubMed] [Google Scholar]
  14. Lander E. S., Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989 Jan;121(1):185–199. doi: 10.1093/genetics/121.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  16. Mangin B., Goffinet B., Rebaï A. Constructing confidence intervals for QTL location. Genetics. 1994 Dec;138(4):1301–1308. doi: 10.1093/genetics/138.4.1301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rebai A., Goffinet B., Mangin B. Comparing power of different methods for QTL detection. Biometrics. 1995 Mar;51(1):87–99. [PubMed] [Google Scholar]
  18. Rebaï A., Goffinet B., Mangin B. Approximate thresholds of interval mapping tests for QTL detection. Genetics. 1994 Sep;138(1):235–240. doi: 10.1093/genetics/138.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stuber C. W., Lincoln S. E., Wolff D. W., Helentjaris T., Lander E. S. Identification of genetic factors contributing to heterosis in a hybrid from two elite maize inbred lines using molecular markers. Genetics. 1992 Nov;132(3):823–839. doi: 10.1093/genetics/132.3.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Visscher P. M., Thompson R., Haley C. S. Confidence intervals in QTL mapping by bootstrapping. Genetics. 1996 Jun;143(2):1013–1020. doi: 10.1093/genetics/143.2.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zeng Z. B. Precision mapping of quantitative trait loci. Genetics. 1994 Apr;136(4):1457–1468. doi: 10.1093/genetics/136.4.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES