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Milliken Mercer Thesis 2013.pdf (2.41 MB)

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The Distribution of Single Nucleotide Polymorphisms in Pyoderma Gangrenosum: Biomarker Discovery

Mercer, Heather Milliken
http://rave.ohiolink.edu/etdc/view?acc_num=kent1383769612

Abstract Details

2013, MS, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Pyoderma gangrenosum (PG) is a rare, inflammatory disease marked by reactive, neutrophilic dermatosis. While PG is non-infectious, it is painful, only diagnosed by exclusion of other disorders (Bhat, 2012), and challenging to treat. Thus, there exists a need for discovery of biomarkers that can aid in faster and more reliable diagnosis. Whole-genome genotyping platforms- such as Affymetrix SNP 6.0 chip - offer rapid and comprehensive ways to survey patients' genomes to identify shared genetic polymorphisms as part of the biomarker discovery. In this work we test the hypothesis that PG is caused by genetic variants within the genome that (1) inhibit neutrophil clearance and immune/inflammatory pathways and (2) that a combination of Single Nucleotide Polymorphisms (SNPs) across multiple loci in this pathway may contribute to this dysfunction. We examined a list of 64,997 SNPs found in 9,831 genes that were shared across six PG patients. These genes were examined to determine whether an over-enrichment of immune- and/or inflammation and/or apoptosis variants exists across patients using Gene Ontology tools. Gene Ontology tools provided insight into the functional classifications of these genes and possible connections to PG etiology. The genes found in common between the PG data set and those known to be active in apoptotic and immunity/inflammatory pathways were further analyzed for the potential effects of genetic variation. Those genetic variants located within exons and 5' and 3' untranslated regions in addition to those that cause missense or nonsense were viewed as the most likely to be related to PG as mutations in those regions are most likely to alter protein products. In addition to the aforementioned genetic regions, those SNPS located in non-coding genic regions (potentially regulatory) as well as those from the inter-genic regions were analyzed. The latter category, while currently lacking known functional annotations, may provide insight into the genome function as putative regulatory regions and/or non-coding RNA as suggested by recent endeavors such as the ENCODE project. Analyses resulted in the discovery of an over-enrichment of SNPs within genes functioning within both apoptotic and immune/inflammatory pathways within the PG Data Set in addition to SNPS located in genes that may be integral to the development of PG.
Helen Piontkivska (Advisor)
Eric Mintz (Committee Member)
Gail Fraizer (Committee Member)
Judy Fulton (Committee Member)
124 p.
Bioinformatics; Biology; Genetics
Pyoderma Gangrenosum; SNP; Single Nucleotide Polymorphism; Genetic Variant; Biomarkers

Recommended Citations

Citations

  • Mercer, H. M. (2013). The Distribution of Single Nucleotide Polymorphisms in Pyoderma Gangrenosum: Biomarker Discovery [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1383769612

    APA Style (7th edition)

  • Mercer, Heather. The Distribution of Single Nucleotide Polymorphisms in Pyoderma Gangrenosum: Biomarker Discovery . 2013. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1383769612.

    MLA Style (8th edition)

  • Mercer, Heather. "The Distribution of Single Nucleotide Polymorphisms in Pyoderma Gangrenosum: Biomarker Discovery ." Master's thesis, Kent State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1383769612

    Chicago Manual of Style (17th edition)

kent1383769612
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© 2013, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.