Including copy number variation in association studies to predict genotypic values

The objective of this study was to investigate, both empirically and deterministically, the ability to explain genetic variation resulting from a copy number polymorphism (CNP) by including the CNP, either by its genotype or by a continuous derivation thereof, alone or together with a nearby single nucleotide polymorphism (SNP) in the model. This continuous measure of a CNP genotype could be a raw hybridization measurement, or a predicted CNP genotype. Results from simulations showed that the linkage disequilibrium (LD) between an SNP and CNP was lower than LD between two SNPs, due to the higher mutation rate at the CNP loci. The model R2 values from analysing the simulated data were very similar to the R2 values predicted with the deterministic formulae. Under the assumption that x copies at a CNP locus lead to the effect of x times the effect of 1 copy, including a continuous measure of a CNP locus in the model together with the genotype of a nearby SNP increased power to explain variation at the CNP locus, even when the continuous measure explained only 15% of the variation at the CNP locus

Identification of (non-) Mendelian factors affecting pork production

This thesis describes the analysis of a large experiment in which Chinese Meishan pigs were crossed with pigs from Dutch commercial lines. Three generations of pigs from this experiment were characterized for molecular markers that cover the entire porcine genome. Linkage was studied between these markers and 17 carcass, meat quality, production, and reproduction traits. Among the Quantitative Trait Loci (QTL) that were identified, important effects of genomic imprinting were observed for body composition and growth traits. Genomic imprinting, where only one allele from a specific parent is expressed in the offspring, is generally regarded to be a rare phenomenon, affecting only 1-2 % of all the genes. Following the large imprinting effects that were identified in this study, the characteristics of imprinted genes and their detection were studied in an extensive simulation study. It was concluded that imprinted QTL might remain undetected when only standard Mendelian models are applied. However, extra care must be taken with the design and analysis of experiments to prevent the false detection of imprinting for QTL that are actually Mendelian. It was also demonstrated that the statistical power of a QTL mapping experiment can increase considerably by using identified QTL as cofactors in a multiple QTL analysis. Finally an application of some of the identified QTL in a commercial pig-breeding program were proposed.</p

Phosphorescence-Fluorescence ratio imaging for monitoring the oxygen status during photodynamic therapy

The effectiveness of photodynamic therapy is strongly dependent on the availabilty of oxygen. In the present paper we show that the ratio between photosensitiser phosphorescence and fluorescence is a parameter that can be used to monitor the competition between singlet oxygen production and other processes quenching the photosensitiser triplet state. We present a theoretical basis for the validity of this approach and a series of in vitro imaging experiments