Dataset Information

Analyzing a putative enhancer of optic disc morphology.

ABSTRACT:

Background

Genome-wide association studies have identified the CDC7-TGFBR3 intergenic region on chromosome 1 to be strongly associated with optic disc area size. The mechanism of its function remained unclear until new data on eQTL markers emerged from the Genotype-Tissue Expression project. The target region was found to contain a strong silencer of the distal (800?kb) Transcription Factor (TF) gene GFI1 (Growth Factor Independent Transcription Repressor 1) specifically in neuroendocrine cells (pituitary gland). GFI1 has also been reported to be involved in the development of sensory neurons and hematopoiesis. Therefore, GFI1, being a developmental gene, is likely to affect optic disc area size by altering the expression of the associated genes via long-range interactions.

Results

Distribution of haplotypes in the putative enhancer region has been assessed using the data on four continental supergroups generated by the 1000 Genomes Project. The East Asian (EAS) populations were shown to manifest a highly homogenous unimodal haplotype distribution pattern within the region with the major haplotype occurring with the frequency of 0.9. Another European specific haplotype was observed with the frequency of 0.21. The major haplotype appears to be involved in silencing GFI1repressor gene expression, which might be the cause of increased optic disc area characteristic of the EAS populations. The enhancer/eQTL region overlaps AluJo element, which implies that this particular regulatory element is primate-specific and confined to few tissues.

Conclusion

Population specific distribution of GFI1 enhancer alleles may predispose certain ethnic groups to glaucoma.

SUBMITTER: Babenko V

PROVIDER: S-EPMC7583307 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Analyzing a putative enhancer of optic disc morphology.

Babenko Vladimir V Babenko Roman R Orlov Yuri Y

BMC genetics 20201022 Suppl 1

<h4>Background</h4>Genome-wide association studies have identified the CDC7-TGFBR3 intergenic region on chromosome 1 to be strongly associated with optic disc area size. The mechanism of its function remained unclear until new data on eQTL markers emerged from the Genotype-Tissue Expression project. The target region was found to contain a strong silencer of the distal (800 kb) Transcription Factor (TF) gene GFI1 (Growth Factor Independent Transcription Repressor 1) specifically in neuroendocrin ...[more]

PMID: 33092545

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Project description:PurposeTo investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.MethodsA total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure ?-peripapillary atrophy (PPA) lengths with and without Bruch's membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.ResultsLC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P < 0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P < 0.001), and larger vertical/horizontal tilt angles (vertical, P < 0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P < 0.001) and vertical tilt angle (P < 0.001) were identified as significant.ConclusionsThe presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.

Project description:To demonstrate papillary imaging of eyes with optic disc pits (ODP) or optic disc pit associated maculopathy (ODP-M) with ultrahigh-speed swept-source optical coherence tomography (SS-OCT) at 1.68 million A-scans/s. To generate 3D-renderings of the papillary area with 3D volume-reconstructions of the ODP and highly resolved en face images from a single densely-sampled megahertz-OCT (MHz-OCT) dataset for investigation of ODP-characteristics.A 1.68 MHz-prototype SS-MHz-OCT system at 1050 nm based on a Fourier-domain mode-locked laser was employed to acquire high-definition, 3D datasets with a dense sampling of 1600?×?1600 A-scans over a 45° field of view. Six eyes with ODPs, and two further eyes with glaucomatous alteration or without ocular pathology are presented. 3D-rendering of the deep papillary structures, virtual 3D-reconstructions of the ODPs and depth resolved isotropic en face images were generated using semiautomatic segmentation.3D-rendering and en face imaging of the optic disc, ODPs and ODP associated pathologies showed a broad spectrum regarding ODP characteristics. Between individuals the shape of the ODP and the appending pathologies varied considerably. MHz-OCT en face imaging generates distinct top-view images of ODPs and ODP-M. MHz-OCT generates high resolution images of retinal pathologies associated with ODP-M and allows visualizing ODPs with depths of up to 2.7 mm.Different patterns of ODPs can be visualized in patients for the first time using 3D-reconstructions and co-registered high-definition en face images extracted from a single densely sampled 1050 nm megahertz-OCT (MHz-OCT) dataset. As the immediate vicinity to the SAS and the site of intrapapillary proliferation is located at the bottom of the ODP it is crucial to image the complete structure and the whole depth of ODPs. Especially in very deep pits, where non-swept-source OCT fails to reach the bottom, conventional swept-source devices and the MHz-OCT alike are feasible and beneficial methods to examine deep details of optic disc pathologies, while the MHz-OCT bears the advantage of an essentially swifter imaging process.

Dataset Information

Analyzing a putative enhancer of optic disc morphology.

Background

Results

Conclusion

Publications

Analyzing a putative enhancer of optic disc morphology.

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