Ben Brett and Dina Ahram will present on Sept 15th in 2-501BSB at noon

Background on Ben Brett’s talk 

Development of Tools and Techniques for Comparative Oncogenomics using Transposon Mutagenesis

 

Cancer is a complex disease normally caused by somatic mutations. To identify these somatic mutations the patient’s genome needs to be sequenced twice, normal and tumor samples. To decrease the cost and difficulty to identify the causative mutations, model organisms can be used. Insertion mutagenesis allows for tissue specific activation and allows for rapid identification of mutation sites. However, the model needs to be validated. This includes identifying clonally expanded integration sites, causative genes, and any biases present in the system. To this end, we determined that the distribution of reads vs integration sitesfits a negative binomial, which can be used to identify clonality cutoffs. Causative genes can be identified by using a combination of a Monte Carlo based simulation and a gene base Chi-Squared test. We have determined that the donor chromosome has more integration than expected by chance and that by identifying the clonal integrations independently, the integrations can be saved Future work will determine if there are any biases in the rest of the genome. 

Background on Dina Ahram’s talk 

Clinical and Genetic Investigation of Familial Angle-Closure Glaucoma in the Basset Hound

Primary angle closure glaucoma (PACG) is an optic neuropathy marked by progressive retinal ganglion cell degeneration, cupping of the optic nerve head and subsequent loss of vision in association with a gradual increase in intraocular pressure (IOP).  The condition is most commonly caused as a result of the collapse of the irido-corneal angle due to the movement of the root of the iris anteriorly towards the cornea. We have identified a number of Basset Hound pedigrees with characteristic PACG that in many aspects recapitulates the clinical PACG phenotype observed in human patients. The condition in Basset Hounds appears at variable ages of onset, segregates in an autosomal recessive manner and displays complete penetrance. Our goal is to utilize the Basset Hound PACG model in order to characterize and better understand the pathophysiology of PACG and its predisposing risk factors. We are uniquely positioned to achieve our goal through a combination of high density mapping of genetic markers, as well as analysis of multiple quantitative traits, copy number variations and gene expression changes in PACG Basset Hound pedigrees, which may enable us to identify the gene or gene network implicated in PACG. Once identified, we aim to characterize the role of this gene in PACG through molecular and protein functional studies. Ultimately, we anticipate for these studies to provide valuable insight into the pathophysiology and genetics of human PACG. 

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