Abstract
Adequate separation of effects of possible multiple linked quantitative trait loci (QTLs) on mapping QTLs is the key to increasing the precision of QTL mapping. A new method of QTL mapping is proposed and analyzed in this paper by combining interval mapping with multiple regression. The basis of the proposed method is an interval test in which the test statistic on a marker interval is made to be unaffected by QTLs located outside a defined interval. This is achieved by fitting other genetic markers in the statistical model as a control when performing interval mapping. Compared with the current QTL mapping method (i.e., the interval mapping method which uses a pair or two pairs of markers for mapping QTLs), this method has several advantages. (1) By confining the test to one region at a time, it reduces a multiple dimensional search problem (for multiple QTLs) to a one dimensional search problem. (2) By conditioning linked markers in the test, the sensitivity of the test statistic to the position of individual QTLs is increased, and the precision of QTL mapping can be improved. (3) By selectively and simultaneously using other markers in the analysis, the efficiency of QTL mapping can be also improved. The behavior of the test statistic under the null hypothesis and appropriate critical value of the test statistic for an overall test in a genome are discussed and analyzed. A simulation study of QTL mapping is also presented which illustrates the utility, properties, advantages and disadvantages of the method.
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Selected References
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- 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]
- 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]
- Jansen R. C. Interval mapping of multiple quantitative trait loci. Genetics. 1993 Sep;135(1):205–211. doi: 10.1093/genetics/135.1.205. [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]
- Paterson A. H., Damon S., Hewitt J. D., Zamir D., Rabinowitch H. D., Lincoln S. E., Lander E. S., Tanksley S. D. Mendelian factors underlying quantitative traits in tomato: comparison across species, generations, and environments. Genetics. 1991 Jan;127(1):181–197. doi: 10.1093/genetics/127.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Weller J. I. Maximum likelihood techniques for the mapping and analysis of quantitative trait loci with the aid of genetic markers. Biometrics. 1986 Sep;42(3):627–640. [PubMed] [Google Scholar]
- Zeng Z. B. Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10972–10976. doi: 10.1073/pnas.90.23.10972. [DOI] [PMC free article] [PubMed] [Google Scholar]