Swati Shimpi

Abstract

SERPINE2 is a genetic marker of Chronic Obstructive Pulmonary Disease (COPD), which is a complex human disease and has no cure. In COPD patients three distinct pathology features, Emphysema, Chronic bronchitis and bronchus- associated lymphoid tissue or BALT like lesions, are observed. SERPINE2 deficient mouse was studied in Mariani lab to find association of SERPINE2 with COPD. This mouse model emulates the lungs of COPD and mimics the lesions of BALT in COPD, with excessive lymphocytes. A total of six samples, three knock out and three age - matched wild type, were used for differential gene expression analysis by Microarray. Multiple methods (PLIER, RMA and MAS5) were used to extract and normalize the previously generated expression data. Multiple analytical approaches, Significance Analysis of Microarray (SAM) at FDR < 5% and T-Test at P-value < 0.05 + fold change of 1.5 up or down, were used to find significantly differently expressed genes. At FDR < 5%, SAM identified seven genes common and T-Test at P-value < 0.05 + FC of 1.5 identified 26 genes common in all three versions of data methods (PLIER, RMA and MAS5). The combined gene selection approach (SAM and T-Test + FC), identified 12 genes (CD247, CYR61, IGHM, FLNB, FSCN1, NFKBIE, PDE4B, RAC2, STAT1, CLIC5, NRAS and SERPINE2) common in all three versions of data and out of these two were validated by qPCR. DAVID and IPA were used to detect gene ontology and canonical pathways associated with significantly different genes. Both pathway detection approaches detected numerous known and novel COPD related pathways such as inflammation, T and B cell development, lymphocytes and immune response. The genes and pathways detected from the study may serve as potential markers of COPD and may provide insights to study the etiology of COPD.

Library of Congress Subject Headings

Genetic markers; Lungs--Diseases, Obstructive; Human genetics

Publication Date

5-15-2012

Document Type

Thesis

Department, Program, or Center

Thomas H. Gosnell School of Life Sciences (COS)

Advisor

Skuse, Gary

Advisor/Committee Member

Reyes, Vicente

Advisor/Committee Member

Mariani, Thomas

Comments

Note: imported from RIT’s Digital Media Library running on DSpace to RIT Scholar Works. Physical copy available through RIT's The Wallace Library at: QH438.4.B55 S45 2012

Campus

RIT – Main Campus

Download

Share

COinS