Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.
Abstract
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.
Type
Journal articleSubject
Science & TechnologyLife Sciences & Biomedicine
Ophthalmology
keratoconus
RNA-seq
coding RNAs
LncRNAs
cornea
GENOME-WIDE ASSOCIATION
HUMAN-DISEASE
PENETRATING KERATOPLASTY
SIGNALING PATHWAYS
GENES
EYE
SEQ
IDENTIFICATION
DISRUPTION
EPITHELIUM
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https://hdl.handle.net/10161/17225Published Version (Please cite this version)
10.1167/iovs.18-24267Publication Info
Khaled, Mariam Lofty; Bykhovskaya, Yelena; Yablonski, Sarah ER; Li, Hanzhou; Drewry,
Michelle D; Aboobakar, Inas F; ... Liu, Yutao (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Robert Rand Allingham
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.
Michael Arthur Hauser
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
Yutao Liu
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
W Daniel Stamer
Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology
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