Specific correlation between the major chromosome 10q26 haplotype conferring risk for age-related macular degeneration and the expression of HTRA1.
Year: 2017
Type: article
Abstract: PURPOSE: A region within chromosome 10q26 has a set of single nucleotide polymorphisms (SNPs) that define a haplotype that confers high risk for age-related macular degeneration (AMD). We used a bioinformatics approach to search for genes in this region that may be responsible for risk for AMD by assessing levels of gene expression in individuals carrying different haplotypes and by searching for open chromatin regions in the retinal pigment epithelium (RPE) that might include one or more of the SNPs. METHODS: We surveyed the PubMed and the 1000 Genomes databases to find all common (minor allele frequency > 0.01) SNPs in 10q26 strongly associated with AMD. We used the HaploReg and LDlink databases to find sets of SNPs with alleles in linkage disequilibrium and used the Genotype-Tissue Expression (GTEx) database to search for correlations between genotypes at individual SNPs and the relative level of expression of the genes. We also accessed Encyclopedia of DNA Elements (ENCODE) to find segments of open chromatin in the region with the AMD-associated SNPs. Predicted transcription factor binding motifs were identified using HOMER, PROMO, and RegulomeDB software programs. RESULTS: ; none of these SNPs affects the risk for AMD according to published genome-wide association studies (GWASs). Two of the AMD-risk SNPs (rs36212732 and rs36212733) affect transcription factor binding sites in proximity to a DNase I hypersensitive region (i.e., a region of open chromatin) in RPE cells. CONCLUSIONS: activity might be a potential therapy for AMD.
Source: Europe PMC (PubMed Central)
Authors: Sha-Mei Liao, Wei Zheng, Jiang Zhu, Casey A Lewis, Omar Delgado, Maura A Crowley, Natasha M Buchanan, Bruce D Jaffee, Thaddeus P Dryja
Institution: Novartis Institutes for BioMedical Research
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Methods for high-resolution analysis of genetic effects on gene expression, Identification and validation of cell specific eQTLs by Bayesian modeling, Using the Transcriptome for SNP and Gene Annotation, MODELING THE EFFECTS OF STRUCTURAL VARIATION IN GTEX DATA AND MENDELIAN DISEASE, Epigenetic Marks of Cocaine Addiction, Genetic Regulation of Gene Expression and its Impact on Phenotypes, Systems approaches to link tissue-specific expression to disease, Harnessing GTEx to Create Transcriptome Knowledge and Inform Disease Biology, Epistatic and Cross Tissue Analysis for Human Gene Expression Traits, Statistical analysis of gene expression quantitative trait loci (eQTL), Methods for high-resolution analysis of genetic effects on gene expression, FACILITATING GTEx, DISEASE, AND GxE ANALYSES VIA FAST EXPRESSION (e)QTL MAPPING, Statistical analysis of gene expression quantitative trait loci (eQTL), CNS Mechanisms in Cocaine-Related Sudden Death
OpenAlex ID: W2625356388