Presenting Author: Kayleigh R Diveley
, Genetics, PhD Candidate at North Carolina State Univ. Col. of Vet. Med.
Abstract:
Many genetic variations in the Fc gamma receptor (FCGR) region have been associated by genome-wide association studies (GWAS) to complex disease and treatment efficacy. However, the genetic complexity exhibited within the human FCGR region presents a challenge for post-GWAS functional analyses. Therefore, the identity and regulatory role of functional Single Nucleotide Polymorphisms (fSNPs) in the FCGR region have been limited to date.
Using the high-throughput Regulatory Element (REEL)-Seq screen, we have systematically identified 549 candidate FCGR fSNPs in THP-1 human monocytes. Several candidate fSNPs with associated immune relevance were selected for further functional characterization and displayed both allele-specific protein interactions and alterations to transcriptional activity of a reporter protein in vitro. These observations lend support to the hypothesis that non-coding variations may influence transcriptional regulation of genes in the FCGR region. To evaluate this hypothesis further, we have utilized CRISPR and CRISPRi systems to edit fSNP locations and perturb their interacting proteins to examine the effects upon FCGRs in THP-1 cells. As FCGR abundance may influence monocyte-based antibody-dependent cellular phagocytosis (ADCP) activity, understanding the regulatory impact of these fSNPs may inform the development of antibody-based therapies and prevention.
Using High-Throughput Approaches To Identify Functional Fc Gamma Receptor SNPs.
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1