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THE ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS IN INTRONIC REGIONS OF ISLET CELL AUTOANTIGEN 1 AND TYPE 1 DIABETES MELLITUS

Blout, Carrie Lynn (2006) THE ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS IN INTRONIC REGIONS OF ISLET CELL AUTOANTIGEN 1 AND TYPE 1 DIABETES MELLITUS. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Type 1 diabetes mellitus is a multifactorial autoimmune disease caused by a combination of genetic and environmental factors. Further knowledge and understanding about the genes which play a role in type 1 diabetes has a clear public health significance in that it will aid in the prediction, treatment and a possible cure. Type 1 diabetes is a chronic disease with a lengthy preclinical course, which eventually results in pancreatic beta cell destruction and inability of the body to produce insulin hormone. Type 1 diabetic patients generally require exogenous insulin to survive. Several genetic loci have been proposed to be linked to type 1 diabetes; however, the HLA and VNTR regions are currently believed to account for the majority of genetic risk, contributing to about 42% and 10% of an individual's risk to develop type 1 diabetes, respectively. This study focuses on the candidate gene Islet Cell Autoantigen 1 (ICA1), which codes for the protein ICA69. This protein product is expressed in the islets of Langerhans, the neuroendocrine system and in the thymic medulla; this last location is an area of the body known to play a major role in immunologic tolerance. Preliminary studies in the NOD and B6 mouse models suggest that a SNP within the promoter region of Ica1 affects transcription and may account for altered expression in the thymus. Our current study aimed to determine whether single nucleotide polymorphisms within intronic regions of the human ICA1 gene differed between a diabetic case population and non-diabetic controls. It was hypothesized that SNPs within the ICA1 gene differ between cases and controls and play a role in the onset of type 1 diabetes. Polymerase Chain Reaction (PCR) was applied for DNA amplification and the pyrosequencing technique was used to genotype all samples. At SNP location rs2058519 there was a clear genotypic difference between the cases and controls (p= .0003). These results suggest that genetic variation at this specific SNP location in the ICA1 may be associated with type 1 diabetes susceptibility. The ultimate goal of this study is to determine whether our candidate gene ICA1 appears to play a role in the pathogenesis of type 1 diabetes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Blout, Carrie Lynncarrie.blout@hgen.pitt.edu
Date: 1 June 2006
Date Type: Completion
Defense Date: 30 March 2006
Approval Date: 1 June 2006
Submission Date: 10 April 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Diabetes; ICA1; ICA69; Single Nucleotide Polymorphisms; SNPs; Type 1 Diabetes
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04102006-140611/, etd-04102006-140611
Date Deposited: 10 Nov 2011 19:35
Last Modified: 15 Nov 2016 13:39
URI: http://d-scholarship.pitt.edu/id/eprint/6945

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