Erin & Lea to Present @ Student Seminar on 12.18.08
Posted by erik
Background to Erin Burnight’s presentation:
The research interests in the McCray Lab focus on innate immunity and therapeutic gene transfer for monogenic diseases, specifically Cystic Fibrosis (CF) and Hemophilia A. I am involved with a project that aims to improve gene transfer to the airway epithelia and ultimately correct the ion imbalance associated the CF defect. CF displays an autosomal recessive pattern of inheritance and about 1 in 3000 babies in the U.S. are born with the disease. The pathogenesis of the disease occurs mainly in the airway and gut with most of the morbidity and mortality resulting from bacterial colonization and invasion in the airways. The genetic etiology of CF is from one of several mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) whose protein product functions at the membrane as an ion channel. Defective CFTR protein cannot traffick properly and the result is a mis-regulated ion gradient that causes a thick mucous build-up in the airway due to impaired mucociliary clearance. CFTR gene transfer to the airway epithelia has demonstrated functional correction of the chloride transport defect in CFTR-null cells. Our lab employs the Feline Immunodeficiency Virus (FIV) to deliver CFTR and various reporter transgenes to cells (primary and immortalized) and animals (mice and pigs.) One of the questions we are trying to address is that of which cell types are important in the pathogenesis of the disease and how can we target specific cell types to achieve therapeutic correction. My project involves utilizing FIV vectors with various cell/tissue-specific internal promoters to direct transgene expression to specific cells or tissues.
erik’s note: Erin has published on gene transfer three previous times.
Background to Lea Davis’s presentation
Copy number variation (CNV) has been operationally defined as insertions and deletions in the genome that are more than 1 kb and not a result of transposable elements. The emergence of DNA microarray technology has enabled detection of CNVs, which has since been found to be both common and relevant to human diseases, including autism. CNVs can be both polymorphic in the general population and associated with disease in particular cases. For example, deletions and duplications of various sizes are known to cause a number of genetically “simple” (single locus) diseases, including Sotos syndrome, Prader-Willi/Angelman syndrome, and Williams-Beuren syndrome. More recently, CNVs have been found to contribute to genetically complex disorders, including glomerulonephritis, quantitative reading phenotypes, autism, schizophrenia, and susceptibility to HIV-1 infection. My work in the Wassink lab typically focuses on copy number variation in autism, however a recent collaboration between Kacie Meyer (Wassink Lab), Emily Schindler (Stone Lab), and myself has taken my work in a new direction. We are working on copy number analysis of 400 individuals with glaucoma, 400 individuals with AMD and 100 age-matched controls. The first phase of this analysis involved detecting CNVs from either 250K SNP arrays or 5.0 SNP arrays. We then identified CNVs that were present at least twice in one group (glaucoma or AMD) and absent from the other group. The second phase of this work includes validation of the CNVs by qPCR or comparative genomic hybridization (CGH) array and comprehensive screening of a replication cohort for the two CNVs with the highest level of enrichment. The final phase of this project includes gathering expression and rt-PCR data from patient fibroblast cell lines for these CNVs. I will present CNV data from the first phase of the study.
erik’s note: Lea has published twice before on autism and autism-related genetics.
Posted on December 17, 2008, in Student Seminar and tagged age-related macular degeneration, AMD, Angelman Syndrome, autism, CNV, Copy number variation, cystic fibrosis, Erin B., FIV, glaucoma, glomerulonephritis, hemophilia a, innate immunity, Lea D., Prader-Willi, schizophrenia, Sotos Syndrome, Williams-Beuren Syndrome. Bookmark the permalink. Leave a comment.