Abstract
A common departure from the usual normality assumption in QTL mapping concerns a spike in the phenotype distribution. For example, in measurements of tumor mass, some individuals may exhibit no tumors; in measurements of time to death after a bacterial infection, some individuals may recover from the infection and fail to die. If an appreciable portion of individuals share a common phenotype value (generally either the minimum or the maximum observed phenotype), the standard approach to QTL mapping can behave poorly. We describe several alternative approaches for QTL mapping in the case of such a spike in the phenotype distribution, including the use of a two-part parametric model and a nonparametric approach based on the Kruskal-Wallis test. The performance of the proposed procedures is assessed via computer simulation. The procedures are further illustrated with data from an intercross experiment to identify QTL contributing to variation in survival of mice following infection with Listeria monocytogenes.
Full Text
The Full Text of this article is available as a PDF (244.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boyartchuk V. L., Broman K. W., Mosher R. E., D'Orazio S. E., Starnbach M. N., Dietrich W. F. Multigenic control of Listeria monocytogenes susceptibility in mice. Nat Genet. 2001 Mar;27(3):259–260. doi: 10.1038/85812. [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]
- Hunter K. W., Broman K. W., Voyer T. L., Lukes L., Cozma D., Debies M. T., Rouse J., Welch D. R. Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 2001 Dec 15;61(24):8866–8872. [PubMed] [Google Scholar]
- Kruglyak L., Lander E. S. A nonparametric approach for mapping quantitative trait loci. Genetics. 1995 Mar;139(3):1421–1428. doi: 10.1093/genetics/139.3.1421. [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]
- Lincoln S. E., Lander E. S. Systematic detection of errors in genetic linkage data. Genomics. 1992 Nov;14(3):604–610. doi: 10.1016/s0888-7543(05)80158-2. [DOI] [PubMed] [Google Scholar]
- McIntyre L. M., Coffman C. J., Doerge R. W. Detection and localization of a single binary trait locus in experimental populations. Genet Res. 2001 Aug;78(1):79–92. doi: 10.1017/s0016672301005092. [DOI] [PubMed] [Google Scholar]
- Rowe L. B., Nadeau J. H., Turner R., Frankel W. N., Letts V. A., Eppig J. T., Ko M. S., Thurston S. J., Birkenmeier E. H. Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm Genome. 1994 May;5(5):253–274. doi: 10.1007/BF00389540. [DOI] [PubMed] [Google Scholar]
- Wittenburg Henning, Lammert Frank, Wang David Q-H, Churchill Gary A., Li Renhua, Bouchard Guylaine, Carey Martin C., Paigen Beverly. Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Physiol Genomics. 2002 Feb 11;8(1):67–77. doi: 10.1152/physiolgenomics.00097.2001. [DOI] [PubMed] [Google Scholar]
- Xu S., Atchley W. R. Mapping quantitative trait loci for complex binary diseases using line crosses. Genetics. 1996 Jul;143(3):1417–1424. doi: 10.1093/genetics/143.3.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]