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Chunk #12 — HIGH‐THROUGHPUT IDENTIFICATION OF SNPs AFFECTING GENE REGULATION

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5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.
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both SH‐SY5Y and SK‐N‐BE (2) cell lines was the same in 25 loci. Eighteen of these 25 SNPs were in eQTLs as defined in the GTEx database, 21 7 lay within binding sites of ELAVL1 (ELAV‐like RNA binding protein 1), 11 within the binding site of PABPC1 (polyA‐binding protein cytoplasmic 1), and 4 SNPs alter the target regions of 13 miRNAs expressed in brain. 22 Another study, testing for the potential function of a set of variants that were identified in meta‐analyses of alcohol‐related traits in African American and European Americans, identified dozens of SNPs that reside in the binding sites of miRNAs and RNA‐binding proteins, and are expression quantitative trait loci of genes including KIF6, FRMD4A, CADM2, ADD2, PLK2, and GAS7. 23 The PASSPORT‐seq assay was recently expanded to test the impact on gene expression of 13,515 SNPs in 3′UTRs in both neuronal (SH‐SY5Y) and microglial (HMC3) cell lines (in preparation). To complement the studies of 3′UTR variants, we have begun to examine the impacts of SNPs in putative enhancer regions on gene expression, using the STARR‐seq approach. 24 The results of these HTRAs will then be used to predict which other SNPs should affect gene expression, and the