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Title page for ETD etd-12102010-133202

Type of Document Dissertation
Author Grayson, Britney L
URN etd-12102010-133202
Title Gene expression and copy number variation in common complex diseases
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Luc Van Kaer Committee Chair
James W. Thomas Committee Member
Marylyn D. Ritchie Committee Member
Nancy Brown Committee Member
Thomas M. Aune Committee Member
  • gene expression
  • copy number variation
  • rheumatoid arthritis
  • diabetes
  • metabolic syndrome
  • genomics
  • complex disease
Date of Defense 2010-09-22
Availability unrestricted
Common, complex diseases are not caused by a single gene mutation but rather have genetic and environmental components. As a subset, autoimmune diseases also possess robust gene expression signatures that have both genetic and environmental contributions. We explored gene expression signatures in type 2 diabetes, coronary artery disease, and their precursor state metabolic syndrome, and identified overlapping gene expression signatures exhibiting greater resemblance to each other than to an autoimmune disease. These signatures are consistent with activation of the innate immune response. Genetic variations contribute to familiality and we sought to determine if large-scale genomic variants, copy number variants (CNVs), are associated with common, complex diseases. To do so, we first developed methods to identify CNVs from SNP-based arrays. We analyzed genomic variation in type 1 diabetes and identified CNVs that were differentially present in patients with or at high risk for type 1 diabetes versus control. Thus, we conclude that both gene expression profiles and genomic variants are easily detected clinical markers that may be useful predictors of disease liability and serve to identify new classes of therapeutic targets.
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  01_GraysonBL_Dissertation.pdf 1.63 Mb 00:07:31 00:03:52 00:03:23 00:01:41 00:00:08
  02_Supplemental_Table_2-1.xls 462.34 Kb 00:02:08 00:01:06 00:00:57 00:00:28 00:00:02
  03_Supplemental_Table_2-2.xls 19.89 Mb 01:32:03 00:47:20 00:41:25 00:20:42 00:01:46
  04_Supplemental_Table_3-1.xls 4.81 Mb 00:22:16 00:11:27 00:10:01 00:05:00 00:00:25
  05_Supplemental_Table_3-2.xls 138.75 Kb 00:00:38 00:00:19 00:00:17 00:00:08 < 00:00:01
  06_Supplemental_Table_4-1.xls 3.08 Mb 00:14:16 00:07:20 00:06:25 00:03:12 00:00:16
  07_Supplemental_Table_4-2.xls 42.50 Kb 00:00:11 00:00:06 00:00:05 00:00:02 < 00:00:01

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