title: Methodology and accuracy of estimation of quantitative trait loci parameters in a half-sib design using maximum likelihood.
abstract: Maximum likelihood methods were developed for estimation of the six parameters relating to a marker-linked quantitative trait locus (QTL) segregating in a half-sib design, namely the QTL additive effect, the QTL dominance effect, the population mean, recombination between the marker and the QTL, the population frequency of the QTL alleles, and the within-family residual variance. The method was tested on simulated stochastic data with various family structures under two genetic models. A method for predicting the expected value of the likelihood was also derived and used to predict the lower bound sampling errors of the parameter estimates and the correlations between them. It was found that standard errors and confidence intervals were smallest for the population mean and variance, intermediate for QTL effects and allele frequency, and highest for recombination rate. Correlations among standard errors of the parameter estimates were generally low except for a strong negative correlation (r = -0.9) between the QTL's dominance effect and the population mean, and medium positive and negative correlations between the QTL's additive effect and, respectively, recombination rate (r = 0.5) and residual variance (r = -0.6). The implications for experimental design and method of analysis on power and accuracy of marker-QTL linkage experiments were discussed.
authors.affiliation: Institute of Cell, Animal and Population Biology, University of Edinburgh, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mackinnon
authors.forename: J I
authors.initials: JI
authors.lastname: Weller
mesh_terms: D000483:Alleles; D000818:Animals; D016001:Confidence Intervals; D003433:Crosses, Genetic; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008433:Mathematics; D008957:Models, Genetic; D015233:Models, Statistical; D009679:Nuclear Family; D011336:Probability; D013269:Stochastic Processes
chemical_list: D005819:Genetic Markers