student profile: Miss Pamela Soh


Thesis work

Thesis title: Investigation of Lymphoma in Border Collies

Supervisors: Mehar KHATKAR , Peter WILLIAMSON , Rosanne TAYLOR

Thesis abstract:

Lymphoma is a common cause of mortality in dogs. Dog breeds are distinct genetic isolates that have varied susceptibility to lymphoma. Examining a single breed reduces biological variation and thus offers a unique opportunity to identify risk factors that contribute to lymphoma. Findings from our study have potential applicability to human lymphoma, since canines and humans have a shared environment, and have similar cancer morphology, progression, response to treatment, and outcome. Broadly, our study has three main aims: 1) to identify genetic risk factors for lymphoma to improve breeding decisions and reduce the frequency of risk allele(s) in the population; 2) to examine biochemical pathways affected by lymphoma through metabolomics; and 3) to investigate potential biomarkers in the serum proteome that may be indicative of lymphoma.�br /� �br /� We will utilise the Illumina Canine Beadchip (173k to 230k markers) and whole genome sequencing of healthy and lymphoma-affected Border Collies to detect associations between genomic regions and the incidence of lymphoma. We will also compare a candidate region for lymphoma in Bullmastiffs, previously identified by our lab, to the Border Collie genotype data to investigate any similar genetic mechanisms for lymphoma in both breeds.�br /� �br /� Genetics alone cannot account for the phenotype of an organism. Due to alterations in gene expression from microRNA species, alternative splicing, and a number of different post-translational modifications, proteins have extensive variation and complexity which contribute to an organism’s phenotype. Proteomic studies provide direct measurements of expression levels that result in a phenotype, and can assist in understanding the pathogenesis of a disease. Similarly, metabolites are direct signatures of biochemical pathways contributing to a phenotype, and understanding the pathways affected by disease could potentially identify new targets for treatments. Few studies in veterinary research have used mass spectrometry to identify proteomic and metabolomic biomarkers for lymphoma. Early detection of biomarkers involved in lymphoma in dogs, as identified through mass spectrometry, can enable early diagnosis of type and stage of cancer, and in turn affect treatments given to improve patient outcome overall.�br /� �br /� We will be conducting a pilot study to profile the plasma metabolome of Border Collies, which will be compared to that of Bullmastiffs, for which samples are available both pre- and post-lymphoma. This will identify any breed-associated differences or shared metabolic pathways when a dog is affected by lymphoma. Lastly, we will investigate the plasma proteome of Border Collies and Bullmastiffs to validate previous studies or potentially identify novel biomarkers for lymphoma.

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