Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.
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2018-06
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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.
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Khaled, Mariam Lofty, Yelena Bykhovskaya, Sarah ER Yablonski, Hanzhou Li, Michelle D Drewry, Inas F Aboobakar, Amy Estes, X Raymond Gao, et al. (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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Scholars@Duke

Michael Arthur Hauser
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 Center, Dr. Hauser is currently conducting a genome wide association study for glaucoma in individuals of African ancestry. These investigations include large datasets collected in Ghana, Nigeria, and South Africa.
Dr. Hauser is also involved in collaborative investigations into the genetics of post-tramatic stress disorder in US veterans from Iraq and Afghanistan. Major collaborators include Dr. Allison Ashley Koch, Dr. Jean Beckham, Dr. Christine Marx and the MIRECC Collaborative group at the Durham Veteran's Administration. We have published a genome wide association study, as well as numerous investigations into candidate genes. Epigenomic DNA methylation analysis and gene expression analysis of 3500 individuals is currently ongoing.

Yutao Liu
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 Institute and Glaucoma Research Foundation to study the effects of DNA copy number variants (CNV) in glaucoma. This research is currently funded by American Health Assistance Foundation (AHAF). The research for exfoliation glaucoma is currently supported by The Glaucoma Foundation (TGF). He is currently characterizing genetic risk variants identified through large scale genome-wide association studies (GWAS) using bioinformatics, molecular genetics, and animal models. He is also interested in applying next-generation sequencing, such as exome sequencing, to identify genetic mutations in multiplex families affected by ocular disorders, such as keratoconus.
Dr. Liu is also the Director of Duke Molecular Genomics Core (MGC) lab(http://wwwchg.duhs.duke.edu/research/molecular.html). The MGC is a state-of-the-art facility that offers a variety of experimental platforms to facilitate genomics research, including but not limited to gene expression profiling for mRNA and microRNA, DNA genotyping, next generation DNA/RNA sequencing, and DNA methylation profiling. For more information, please visit the MGC website (http://wwwchg.duhs.duke.edu/research/molecular.html).
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