Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-17T16:15:41.907Z Has data issue: false hasContentIssue false

Detection of quantitative trait loci from frequency changes of marker alleles under selection

Published online by Cambridge University Press:  14 April 2009

Peter D. Keightley*
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
Grahame Bulfield
Affiliation:
AFRC Roslin Institute (Edinburgh), Roslin, Midlothian, EH25 9PS, Scotland
*
* Corresponding author
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

A method was developed to estimate effects of quantitative trait loci (QTL) by maximum likelihood using information from changes of gene frequency at marker loci under selection, assuming an additive model of complete linkage between markers and QTL. The method was applied to data from 16 molecular and coat colour marker loci in mouse lines derived from the F2 of two inbred strains which were divergently selected on 6-week weight for 21 generations. In 4 regions of the genome, marker allele frequencies were more extreme than could be explained by sampling, implying selection at nearby QTL. An effect of about 0·5 standard deviations was located on chromosome 11, and accounted for nearly 10% of the genetic variance in the base population. QTL with effects as small as 0·2 phenotypic standard deviations could be detected. For typing of a given number of individuals, the power of detection of QTL is very high compared to, for example, analysis of an F2 population. The joint effects of linkage and selection were investigated by Monte Carlo simulation. Marker gene frequencies change little as a consequence of selection at a QTL unless the marker and QTL are less than about 20 cM apart.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1993

References

Blatt, C., Mileham, K., Haas, M., Nesbitt, M. N., Harper, M. E. & Simon, M. I. (1983). Chromosomal mapping of the mink cell focus-inducing and xenotropic env gene family in the mouse. Proceedings of the National Academy of Science USA 80, 62986302.CrossRefGoogle ScholarPubMed
Bulfield, G. & Bantin, G. (1981). Genetic monitoring of inbred strains of mice using electrophoresis and electro-focusing. Laboratory Animals 15, 147149.Google Scholar
Church, G. M. & Gilbert, W. (1984). Genomic sequencing. Proceedings of the National Academy of Science, USA 81, 19911995.Google Scholar
Cornall, R. J., Aitman, T. J., Hearne, C. M. and Todd, J. A. (1991). The generation of a library of PCR-analyzed microsatellite variants for genetic mapping of the mouse genome. Genomics 10, 874881.CrossRefGoogle ScholarPubMed
Darvasi, A., Weinreb, A., Minke, V., Weller, J. I. & Soller, M. (1993). Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. Genetics 134, 943951.Google Scholar
Dietrich, W., Katz, H., Lincoln, S. E., Shin, H.-S., Friedman, J., Dracopoli, N. & Lander, E. S. (1992). A genetic map of the mouse suitable for typing interspecific crosses. Genetics 131, 423447.Google Scholar
DuMouchel, W. H. & Anderson, W. W. (1968). The analysis of selection in experimental populations. Genetics 58, 435449.Google Scholar
Falconer, D. S. (1973). Replicated selection for body weight in mice. Genetical Research 22, 291321.CrossRefGoogle ScholarPubMed
Falconer, D. S. (1989). Introduction to Quantitative Genetics, 3rd edn.London: Longman.Google Scholar
Feinberg, A. P. & Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Analytical Biochemistry 132, 6.Google Scholar
Frankel, W. N., Stoye, J. P., Taylor, B. A. & Coffin, J. M. (1989a). Genetic analysis of endogenous xenotropic murine leukemia viruses: association with two common mouse mutations and the viral restriction locus Fv-I. Journal of Virology 63, 17631774.Google Scholar
Frankel, W. N., Stoye, J. P., Taylor, B. A. & Coffin, J. M. (1989b). Genetic identification of endogenous polytropic proviruses by using recombinant inbred mice. Journal of Virology 63, 38103821.CrossRefGoogle ScholarPubMed
Frankel, W. N., Stoye, J. P., Taylor, B. A. & Coffin, J. M. (1990). A linkage map of endogenous murine leukemia proviruses. Genetics 124, 221236.CrossRefGoogle ScholarPubMed
Garnett, I. & Falconer, D. S. (1975). Protein variation in strains of mice differing in body size. Genetical Research 25, 4557.CrossRefGoogle ScholarPubMed
Georges, M. (1993). Mapping Quantitative trait loci affecting milk production using a primary bovine DNA marker map. Proceedings of the Seventeenth International Congress of Genetics, Birmingham.Google Scholar
Green, C. V. (1935). Apparent changes with age in X-over between colour and size genes in mice. Journal of Genetics 30, 101106.CrossRefGoogle Scholar
Hedrick, P. W. & Comstock, R. E. (1968). Role of linkage in gene frequency changes of coat color alleles in mice. Genetics 58, 297303.Google Scholar
Holland, C. A., Wozney, J. & Hopkins, N. (1983). Nucleotide sequence of the gp70 gene of murine retrovirus MCF 247. Journal of Virology 47, 413420.Google Scholar
Jabob, H. J., Lindpainter, K., Lincoln, S. E., Kusumi, K., Bunker, R. K., Mao, Y.-P., Ganten, D., Dzau, V. J. & Lander, E. S. (1991). Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67, 213224.Google Scholar
Lebowitz, R. J., Soller, M. & Beckmann, J. S. (1987). Trait-based analyses for the detection of linkage between marker loci and quantitative trait loci in crosses between inbred lines. Theoretical and Applied Genetics 73, 556562.Google Scholar
Love, J. M., Knight, A. M., McAleer, M. A. & Todd, J. A. (1990). Towards construction of a high resolution map of the mouse genome using PCR analysed microsatellites. Nucleic Acids Research 18, 41234130.Google Scholar
Paterson, A. H., Lander, E. S., Hewitt, J. D., Peterson, S., Lincoln, S. E. & Tanksley, S. D. (1988). Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature 335, 721726.CrossRefGoogle ScholarPubMed
Patterson, H. D. & Thompson, R. (1971). Recovery of interblock information when block sizes are unequal. Biometrika 58, 545.Google Scholar
Sax, K. (1923). The association of size differences with seed Detection coat pattern and pigmentation in Phaseolus vulgaris. Genetics 8, 552560.Google Scholar
Simpson, E., Bulfield, G., Brenan, M., Fitzpatrick, W., Hetherington, C. & Blann, A. (1982). H-2-associated differences in replicated strains of mice divergently selected for body weight. Immunogenetics 15, 6370.CrossRefGoogle ScholarPubMed
Soller, M. & Beckmann, J. S. (1990). Marker-based mapping of quantitative trait loci using replicated progenies. Theoretical and Applied Genetics 80, 205208.Google Scholar
Stuber, C. W., Lincoln, S. E., Wolff, D. W., Helentjaris, T. & Lander, E. S. (1992). Identification of genetic factors contributing to heterosis in a hybrid from two elite maize inbred lines using molecular markers. Genetics 123, 823839.CrossRefGoogle Scholar
Thoday, J. M. (1961). Location of polygenes. Nature 191, 368370.CrossRefGoogle Scholar
Todd, J. A., Aitman, T. J., Cornall, R. J., Gosh, S., Hall, J. R. S., Hearne, C. M., Knight, A. M., Love, J. M., McAleer, M. A., Prins, J., Rodrigues, N., Lathrop, M., Pressey, A., DeLarato, N. H., Peterson, L. B. & Wicker, L. S. (1991). Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351, 542547.Google Scholar