eP327: A quantitative trait GWAS on lens thickness identifies risk loci on PTPRM in the narrow-angle individuals anatomically susceptible to PACG

Chakraborty, Sudipta; Bhattacharjee, Samsiddhi; Acharya, Moulinath

doi:10.1016/j.gim.2022.01.362

Cited by 1 publication

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“…We specifically queried genomic coordinates chr2:125,083,095-125,084,384 spanning the CNTNAP5 locus for reported CREs characterized by empirical DNaseI, CTCF, H3K4me3, and H3K27ac signals. Data on genomic location, biochemical epigenetic readouts, normal cell/tissue source identifiers and other annotation metadata were systematically compiled for downstream analysis in R software (R, version 4.1.2) environment as described in Chakraborty et al, 2023 14 . The regulatory potential of CNTNAP5 intronic and 3' UTR SNPs was assessed using the DeepSEA web server and RegulomeDB.…”

Section: Integrative Bioinformatic Analysismentioning

confidence: 99%

Post-GWAS functional analyses ofCNTNAP5suggests its role in glaucomatous neurodegeneration

Chakraborty,

Sarma,

Roy

et al. 2024

Preprint

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Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based GWAS, we identified a novelCNTNAP5genic region, significantly associated with PACG. In the current study, we have extended our perception ofCNTNAP5involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role ofCNTNAP5in visual neurodegeneration.

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Section: Integrative Bioinformatic Analysismentioning

confidence: 99%