Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration
Abstract Background Age-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Human Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s40246-019-0199-1 |
| _version_ | 1817996959981502464 |
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| author | Madhu Sudhana Saddala Anton Lennikov Anthony Mukwaya Lijuan Fan Zhengmao Hu Hu Huang |
| author_facet | Madhu Sudhana Saddala Anton Lennikov Anthony Mukwaya Lijuan Fan Zhengmao Hu Hu Huang |
| author_sort | Madhu Sudhana Saddala |
| collection | DOAJ |
| description | Abstract Background Age-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differential gene expression, single-nucleotide polymorphisms (SNPs), indels, and simple sequence repeats (SSRs) in datasets of the human peripheral retina and RPE-choroid-sclera control and AMD. Methods and results Adaptors and unbiased components were removed and checked to ensure the quality of the data sets. Molecular function, biological process, cellular component, and pathway analyses were performed on differentially expressed genes. Analysis of the gene expression datasets identified 5011 upregulated genes, 11,800 downregulated genes, 42,016 SNPs, 1141 indels, and 6668 SRRs between healthy controls and AMD donor material. Enrichment categories for gene ontology included chemokine activity, cytokine activity, cytokine receptor binding, immune system process, and signal transduction respectively. A functional pathways analysis identified that chemokine receptors bind chemokines, complement cascade genes, and create cytokine signaling in immune system pathway genes (p value < 0.001). Finally, allele-specific expression was found to be significant for Chemokine (C-C motif) ligand (CCL) 2, 3, 4, 13, 19, 21; C-C chemokine receptor (CCR) 1, 5; chemokine (C-X-C motif) ligand (CXCL) 9, 10, 16; C-X-C chemokine receptor type (CXCR) 6; as well as atypical chemokine receptor (ACKR) 3,4 and pro-platelet basic protein (PPBP). Conclusions Our results improve our overall understanding of the chemokine receptors’ signaling pathway in AMD conditions, which may lead to potential new diagnostic and therapeutic targets. |
| first_indexed | 2024-04-14T02:31:16Z |
| format | Article |
| id | doaj.art-9166ea592927457c944d46b758831510 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-14T02:31:16Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-9166ea592927457c944d46b7588315102022-12-22T02:17:41ZengBMCHuman Genomics1479-73642019-03-0113111410.1186/s40246-019-0199-1Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degenerationMadhu Sudhana Saddala0Anton Lennikov1Anthony Mukwaya2Lijuan Fan3Zhengmao Hu4Hu Huang5Mason Eye Institute, University of MissouriMason Eye Institute, University of MissouriDepartment of Ophthalmology, Faculty of Health Sciences, Institute for Clinical and Experimental Medicine, Linköping UniversityMason Eye Institute, University of MissouriCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South UniversityMason Eye Institute, University of MissouriAbstract Background Age-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differential gene expression, single-nucleotide polymorphisms (SNPs), indels, and simple sequence repeats (SSRs) in datasets of the human peripheral retina and RPE-choroid-sclera control and AMD. Methods and results Adaptors and unbiased components were removed and checked to ensure the quality of the data sets. Molecular function, biological process, cellular component, and pathway analyses were performed on differentially expressed genes. Analysis of the gene expression datasets identified 5011 upregulated genes, 11,800 downregulated genes, 42,016 SNPs, 1141 indels, and 6668 SRRs between healthy controls and AMD donor material. Enrichment categories for gene ontology included chemokine activity, cytokine activity, cytokine receptor binding, immune system process, and signal transduction respectively. A functional pathways analysis identified that chemokine receptors bind chemokines, complement cascade genes, and create cytokine signaling in immune system pathway genes (p value < 0.001). Finally, allele-specific expression was found to be significant for Chemokine (C-C motif) ligand (CCL) 2, 3, 4, 13, 19, 21; C-C chemokine receptor (CCR) 1, 5; chemokine (C-X-C motif) ligand (CXCL) 9, 10, 16; C-X-C chemokine receptor type (CXCR) 6; as well as atypical chemokine receptor (ACKR) 3,4 and pro-platelet basic protein (PPBP). Conclusions Our results improve our overall understanding of the chemokine receptors’ signaling pathway in AMD conditions, which may lead to potential new diagnostic and therapeutic targets.http://link.springer.com/article/10.1186/s40246-019-0199-1AMDRNA-SeqGene ontologyHuman eyeChemokine receptor |
| spellingShingle | Madhu Sudhana Saddala Anton Lennikov Anthony Mukwaya Lijuan Fan Zhengmao Hu Hu Huang Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration Human Genomics AMD RNA-Seq Gene ontology Human eye Chemokine receptor |
| title | Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration |
| title_full | Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration |
| title_fullStr | Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration |
| title_full_unstemmed | Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration |
| title_short | Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration |
| title_sort | transcriptome wide analysis of differentially expressed chemokine receptors snps and ssrs in the age related macular degeneration |
| topic | AMD RNA-Seq Gene ontology Human eye Chemokine receptor |
| url | http://link.springer.com/article/10.1186/s40246-019-0199-1 |
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