Search

The need for conservation of farm animal genetic resources is widely accepted. A key question is the choice of breeds to be conserved. For this purpose, a core set of breeds was introduced in that the total genetic variance of a hypothetical quantitative trait was maximised (MVT core set). For each breed the relative contribution to the core set was estimated and the breeds were ranked for conservation priority according to their relative contribution. The method was based on average kinships between and within breeds and these can be estimated using genetic marker data. The method was compared to a recently published core set method that maximises the variance of a hypothetical population that could be obtained by interbreeding the conserved breeds (MVO core set). The results show that the MVT (MVO) core set favours breeds with a high (low) within breed kinship that are not related to other breeds. Following this, the MVT core set method suggests conserving breeds that show a large difference in the respective population mean of a hypothetical quantitative trait. This maximises the speed of achieving selection response for this hypothetical selection direction. Additionally, bootstrap based methods for the estimation of the breed's contribution to the core sets were introduced, substantially improving the accuracy of the contribution estimates.

A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD) information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC) methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

The ordinary-, penalized-, and bootstrap $t$-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR), i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-$t$-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped $P$-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-$t$-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

The prediction of identity by descent (IBD) probabilities is essential for all methods that map quantitative trait loci (QTL). The IBD probabilities may be predicted from marker genotypes and/or pedigree information. Here, a method is presented that predicts IBD probabilities at a given chromosomal location given data on a haplotype of markers spanning that position. The method is based on a simplification of the coalescence process, and assumes that the number of generations since the base population and effective population size is known, although effective size may be estimated from the data. The probability that two gametes are IBD at a particular locus increases as the number of markers surrounding the locus with identical alleles increases. This effect is more pronounced when effective population size is high. Hence as effective population size increases, the IBD probabilities become more sensitive to the marker data which should favour finer scale mapping of the QTL. The IBD probability prediction method was developed for the situation where the pedigree of the animals was unknown (i.e. all information came from the marker genotypes), and the situation where, say $T$, generations of unknown pedigree are followed by some generations where pedigree and marker genotypes are known.

The effect of non-random mating on genetic response was compared for populations with discrete generations. Mating followed a selection step where the average coancestry of selected animals was constrained, while genetic response was maximised. Minimum coancestry (MC), Minimum coancestry with a maximum of one offspring per mating pair (MC1) and Minimum variance of the relationships of offspring (MVRO) mating schemes resulted in a delay in inbreeding of about two generations compared with Random, Random factorial and Compensatory mating. In these breeding schemes where selection constrains the rate of inbreeding, $\Delta$ F, the improved family structure due to non-random mating increased genetic response. For schemes with $\Delta$ F constrained to 1.0% and 100 selection candidates, genetic response was 22% higher for the MC1 and MVRO schemes compared with Random mating schemes. For schemes with a less stringent constraint on $\Delta$ F or more selection candidates, the superiority of the MC1 and MVRO schemes was smaller ($5-6$ %). In general, MC1 seemed to be the preferred mating method, since it almost always yielded the highest genetic response. MC1 mainly achieved these high genetic responses by avoiding extreme relationships among the offspring, i.e. fullsib offspring are avoided, and by making the contributions of ancestors to offspring more equal by mating least related animals.