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The availability of genome sequence infonnation for an organism can allow genomic analysis from a chromosomal perspective (chromonomics). Chromonomics encompasses many investigations from karyotype definition to comparative fluorescence in-situ hybridization (FISH), from copy number variation (CNY) to sequence analysis on the chromosomal level. The species of interest in this thesis is the domestic pig (Sus scrota). The pig is an excellent model organism both for the study of various human diseases (both are similar in size and physiology) and from an agricultural perspective (pork is the world's most consumed meat). Fatness is a trait of interest in both disciplines as excess fat can cause many illnesses including heart disease, strokes and cancer. It is a commercially important trait due to the preference of markets for differing fat levels in their meat and the effect of marbling on taste. The aim of this thesis was to provide the most comprehensive "chromonomic" study of the porcine genome to date, specifically: • To use the programme "GenAlyzer" to establish chromosomal syntenies between pig, human and cattle to identify evolutionary breakpoint regions (EBRs), homologous synteny blocks (HSBs) and intrachromosomal translocations (lCTs) between the three species. This was achieved and FISH used to confirm the in-silica analysis for a selection of clones • To develop a means of retrieving sufficient quantities of DNA from archived blood spots to apply to SNP microarray. This was achieved from blood stored on "FTA Whatman cards" and 288 known individuals (96 "fat" and 96 "lean") from Sire Line Large White, Duroc and Titan pigs were interrogated using the IlIumina Porcine SNP60 Genotyping BeadChip • To derive CNV information from the SNP chip raw data, compare analysis algorithms ("QuantiSNP" and "cnvPartition"), provide an overview of CNVs in pigs and ask whether any CNVs are associated with a fatness phenotype. Candidate "fatness CNYs" contain genes including PPARa and MCHRI were implicated. • To perform a Genome wide association study, identify candidate SNPs associated with fatness and devise a means of detecting them easily and cheaply. Five SNPs were identified implicating genes including NTS, FABP6, SST, NR3C2 and GLOI. These "chromonomic" studies of the pig genome provide further insight into genome evolution and gene function in the pig, potentially infonning animal breeding programs. xvii

Given the great promise of High Intensity Focused Ultrasound (HIFU) as a therapeutic modality, the aim of the present study is to develop and optimise a technique that uses externally applied focused ultrasound energy and remote, ultrasound-based treatment monitoring to destroy subcutaneous fat safely, effectively and non-invasively. Based on initial cavitation and temperature measurements performed ex vivo in excised porcine fat at four different frequencies (0.5, 1.1, 1.6 & 3.4MHz) over a range of pressure amplitudes and exposure durations, it was concluded that 0.5MHz is the optimal frequency for this application since it is capable of instigating inertial cavitation at relatively modest pressures while enhancing focal heat deposition. Histological assessment of tissue treated above the cavitation threshold at 0.5MHz both ex vivo and in vivo demonstrated damage to adipocytes and connective tissue. Furthermore, a good correlation was identified between the energy of broadband emissions detected by the passive cavitation detector (PCD) and the focal temperature rise at 0.5MHz during ex vivo experimentation, which could be exploited as a tool for non-invasive monitoring of successful treatment delivery. In addition, localisation of cavitation activity by means of passive cavitation detection was achieved and shown to provide a strong indicator of the location of induced histological damage. Based on the specific requirements identified during initial experimentation, an application-specific HIFU transducer, cavitation detector and real-time treatment monitoring software was developed and tested ex vivo. This treatment system was found capable of producing extensive damage to adipocytes and collagen confined to the subcutaneous fat layer at the desired treatment depth, which coincided with the location of cavitation activity as displayed by the real-time treatment monitoring software.