Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.
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Keratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC.From the corneas of 10 KC patients and 8 non-KC healthy controls, 200 ng total RNA was used to prepare sequencing libraries with the SMARTer Stranded RNA-Seq kit after ribosomal RNA depletion, followed by paired-end 50-bp sequencing with Illumina Sequencer. Differential analysis was done using TopHat/Cufflinks with a gene file from Ensembl and a lncRNA file from NONCODE. Pathway analysis was performed using WebGestalt. Using the expression level of differentially expressed coding and noncoding RNAs in each sample, we correlated their expression levels in KC and controls separately and identified significantly different correlations in KC against controls followed by visualization using Cytoscape.Using |fold change| ≥ 2 and a false discovery rate ≤ 0.05, we identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas. Pathway analysis indicated the enrichment of genes involved in extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Our correlation analysis identified 296 pairs of significant KC-specific correlations containing 117 coding genes enriched in functions related to cell migration/motility, extracellular space, cytokine response, and cell adhesion. Our study highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis.Our RNA-Seq-based differential expression and correlation analyses have identified many potential KC contributing coding and noncoding RNAs.
SubjectScience & Technology
Life Sciences & Biomedicine
Published Version (Please cite this version)10.1167/iovs.18-24267
Publication InfoAboobakar, Inas F; Allingham, Robert Rand; Bykhovskaya, Yelena; Drewry, Michelle D; Estes, Amy; Gao, X Raymond; ... Yablonski, Sarah ER (2018). Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas. Investigative ophthalmology & visual science, 59(7). pp. 2717-2728. 10.1167/iovs.18-24267. Retrieved from https://hdl.handle.net/10161/17225.
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Richard and Kit Barkhouser Professor of Ophthalmology, in the School of Medicine
Dr. Allingham has pursued both basic science and clinical research in the subspecialty of glaucoma. His major research interest is the study of genetic eye disorders, primarily the inherited glaucomas. The most common form of glaucoma (primary open-angle glaucoma or POAG) is believed to have a strong genetic component. He leads a large NIH funded study of which is directed at identifying the specific gene(s) responsible for glaucoma. Over 9,000 individuals have been enrolled in the Duk
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Professor in Medicine
Dr. Hauser has a strong interest in ocular genetics. Genomic studies at the Center for Human Genetics have identified multiple linkage peaks and susceptibility genes in primary open angle glaucoma (POAG) and age related macular degeneration (AMD). Dr. Hauser has recently accepted a 20% appointment at the Singapore Eye Research INstitute and the Duke/National University of Singapore. In collaboration with multiple collaborators in Singapore, and Dr. Rand Allingham at the Duke Eye Cente
Adjunct Assistant Professor in the Department of Medicine
Dr. Liu's research interest is to identify genetic risk factors related to age-related complex human diseases, including but not limited to primary open-angle glaucoma (POAG), keratoconus, exfoliation glaucoma (XFG), amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), and Post-traumatic Stress Disorder (PTSD). Dr. Liu is also interested in the role of genomic structural variation (i.e., DNA copy number variants) in human disease. He was funded by the Duke Translational Medicine Insti
Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology
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