Abstract
A multilocus model for complex traits is described that generalizes the additive and multiplicative models and hence allows simultaneously for both heterogeneity and gene interaction (epistasis). Statistical methods of linkage analysis are discussed under the assumption that identity by descent data from a dense set of polymorphic markers are available. Three methods, single locus search, simultaneous search and conditional search, are described and compared.
Full Text
The Full Text of this article is available as a PDF (1.5 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- Hodge S. E. Some epistatic two-locus models of disease. I. Relative risks and identity-by-descent distributions in affected sib pairs. Am J Hum Genet. 1981 May;33(3):381–395. [PMC free article] [PubMed] [Google Scholar]
- James J. W. Frequency in relatives for an all-or-none trait. Ann Hum Genet. 1971 Jul;35(1):47–49. doi: 10.1111/j.1469-1809.1956.tb01377.x. [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]
- Knapp M., Seuchter S. A., Baur M. P. Two-locus disease models with two marker loci: the power of affected-sib-pair tests. Am J Hum Genet. 1994 Nov;55(5):1030–1041. [PMC free article] [PubMed] [Google Scholar]
- Lander E. S., Botstein D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science. 1987 Jun 19;236(4808):1567–1570. doi: 10.1126/science.2884728. [DOI] [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]
- Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
- Nelson S. F., McCusker J. H., Sander M. A., Kee Y., Modrich P., Brown P. O. Genomic mismatch scanning: a new approach to genetic linkage mapping. Nat Genet. 1993 May;4(1):11–18. doi: 10.1038/ng0593-11. [DOI] [PubMed] [Google Scholar]
- Puffenberger E. G., Kauffman E. R., Bolk S., Matise T. C., Washington S. S., Angrist M., Weissenbach J., Garver K. L., Mascari M., Ladda R. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. 1994 Aug;3(8):1217–1225. doi: 10.1093/hmg/3.8.1217. [DOI] [PubMed] [Google Scholar]
- Risch N. Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):229–241. [PMC free article] [PubMed] [Google Scholar]