Abstract
The determination of empirical confidence intervals for the location of quantitative trait loci (QTLs) was investigated using simulation. Empirical confidence intervals were calculated using a bootstrap resampling method for a backcross population derived from inbred lines. Sample sizes were either 200 or 500 individuals, and the QTL explained 1, 5, or 10% of the phenotypic variance. The method worked well in that the proportion of empirical confidence intervals that contained the simulated QTL was close to expectation. In general, the confidence intervals were slightly conservatively biased. Correlations between the test statistic and the width of the confidence interval were strongly negative, so that the stronger the evidence for a QTL segregating, the smaller the empirical confidence interval for its location. The size of the average confidence interval depended heavily on the population size and the effect of the QTL. Marker spacing had only a small effect on the average empirical confidence interval. The LOD drop-off method to calculate empirical support intervals gave confidence intervals that generally were too small, in particular if confidence intervals were calculated only for samples above a certain significance threshold. The bootstrap method is easy to implement and is useful in the analysis of experimental data.
Full Text
The Full Text of this article is available as a PDF (774.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Cardon L. R., Smith S. D., Fulker D. W., Kimberling W. J., Pennington B. F., DeFries J. C. Quantitative trait locus for reading disability on chromosome 6. Science. 1994 Oct 14;266(5183):276–279. doi: 10.1126/science.7939663. [DOI] [PubMed] [Google Scholar]
- Chiano M. N., Yates J. R. Bootstrapping in human genetic linkage. Ann Hum Genet. 1994 May;58(Pt 2):129–143. doi: 10.1111/j.1469-1809.1994.tb01882.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Fulker D. W., Cardon L. R. A sib-pair approach to interval mapping of quantitative trait loci. Am J Hum Genet. 1994 Jun;54(6):1092–1103. [PMC free article] [PubMed] [Google Scholar]
- Haley C. S., Knott S. A., Elsen J. M. Mapping quantitative trait loci in crosses between outbred lines using least squares. Genetics. 1994 Mar;136(3):1195–1207. doi: 10.1093/genetics/136.3.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Paterson A. H., Lander E. S., Hewitt J. D., Peterson S., Lincoln S. E., Tanksley S. D. Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature. 1988 Oct 20;335(6192):721–726. doi: 10.1038/335721a0. [DOI] [PubMed] [Google Scholar]
- 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]