Quantitative trait locus analysis of hybrid pedigrees: variance-components model, inbreeding parameter, and power.
BACKGROUND
For the last years reliable mapping of quantitative trait loci (QTLs) has become feasible through linkage analysis based on the variance-components method. There are now many approaches to the QTL analysis of various types of crosses within one population (breed) as well as crosses between divergent populations (breeds). However, to analyse a complex pedigree with dominance and inbreeding, when the pedigree's founders have an inter-population (hybrid) origin, it is necessary to develop a high-powered method taking into account these features of the pedigree.


RESULTS
We offer a universal approach to QTL analysis of complex pedigrees descended from crosses between outbred parental lines with different QTL allele frequencies. This approach improves the established variance-components method due to the consideration of the genetic effect conditioned by inter-population origin and inbreeding of individuals. To estimate model parameters, namely additive and dominant effects, and the allelic frequencies of the QTL analysed, and also to define the QTL positions on a chromosome with respect to genotyped markers, we used the maximum-likelihood method. To detect linkage between the QTL and the markers we propose statistics with a non-central chi2-distribution that provides the possibility to deduce analytical expressions for the power of the method and therefore, to estimate the pedigree's size required for 80% power. The method works for arbitrarily structured pedigrees with dominance and inbreeding.


CONCLUSIONS
Our method uses the phenotypic values and the marker information for each individual of the pedigree under observation as initial data and can be valuable for fine mapping purposes. The power of the method is increased if the QTL effects conditioned by inter-population origin and inbreeding are enhanced. Several improvements can be developed to take into account fixed factors affecting trait formation, such as age and sex.
Svischeva
Gulnara R
GR
Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, Lavrentiev Ave, 10, Novosibirsk, 630090, Russia. gulsvi@mail.ru
D000704:Analysis of Variance; D000818:Animals; D002678:Chimera / Q000235:genetics*; D003198:Computer Simulation; D003241:Consanguinity; D006801:Humans; D007178:Inbreeding; D008957:Models, Genetic; D010375:Pedigree; D040641:Quantitative Trait Loci; D012680:Sensitivity and Specificity