We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Abbott Diagnostics- Hematology Division

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Lupus Genetic Risk Variant Allelic Enhancer Activity Discovered

By LabMedica International staff writers
Posted on 31 Mar 2021
Print article
Image: Autoreactive B Cells seen in Systemic Lupus Erythematosus (Photo courtesy of Sebastian Kaulitzki)
Image: Autoreactive B Cells seen in Systemic Lupus Erythematosus (Photo courtesy of Sebastian Kaulitzki)
Systemic lupus erythematosus (SLE) affects about 300,000 people in the USA, the majority of whom are women. Previous studies have implicated both genetic and environmental contributors to the condition. While nearly 100 genetic loci have been associated with lupus, it is also closely tied to previous infection with Epstein-Barr virus.

SLE is a complex disease that involves multiple cell types. Previous systematic studies demonstrate that SLE-risk loci are enriched for B cell-specific genes and regulatory regions. B cells are critical to the pathoetiology of SLE, a disease characterized by autoantibody production. B cells also present self-antigens to T cells in the development of an autoantigen-focused (i.e., “self”) inflammatory response.

A team of Medical Scientists at the Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA) and their colleagues applied a gene screening tool they developed to further investigate genetic loci associated with SLE. Through their massively parallel reporter assay (MPRA) approach, they narrowed in on key disease-linked genetic variants and began to tease out disease-associated biological mechanisms.

The team first conducted linkage disequilibrium expansion analyses in different ancestral groups for the 91 risk loci to capture as many disease-linked variants as possible. In all, they identified 3,073 genetic variants, to which they added a further 20 variants highlighted in a previous study. For each of these, they generated a pair of 170-base-pair DNA oligonucleotides with random 20mers for barcoding and added the eGFR gene under a minimal promoter. In all, they generated 12,478 oligos, which they transfected into an Epstein-Barr virus-transformed B cell line.

The investigators further found that certain transcription factors had altered binding at these SLE risk loci. For instance, the rs3101018 variant, for which the non-risk allele exhibits 1.7-fold stronger enhancer activity, they uncovered 15 proteins that better bound the non-risk allele and two that preferred the risk allele. The ATF7, CREB1, and CREM proteins all bound the non-risk allele more tightly than the risk allele, suggesting that weaker binding to the risk allele could change how other proteins are recruited to the locus and affect the expression of the associated C4A gene. They similarly found changed protein binding at the rs2069235 variant. additionally transfected their SLE MRPA library into the Jurkat cell line of T cells, another key cell type in lupus. In this cell line, they uncovered 92 SLE risk variants that were allelic enhancer variants, a quarter of which were also found in the B cell line.

Leah C. Kottyan, PhD, an Associate Professor and joint senior author of the study, said, “This study not only provides several critical new discoveries about lupus, and it also provides a blueprint for dissecting the genetic mechanisms of many complex human diseases.”

The authors concluded that the MPRA is a robust tool for the nomination of causal genetic risk variants for any phenotype or disease with risk loci that act through genotype-dependent gene regulatory mechanisms, with this study providing a blueprint for dissecting the genetic etiology of many complex human diseases. The study was published on March 12, 2021 in the journal Nature Communications.

Related Links:
Cincinnati Children’s Hospital Medical Center

New
Gold Supplier
Lactate Dehydrogenase (LDH) Assay
LDH 21 FS
New
Silver Supplier
Automated RPR Syphilis Test
Automated RPR Test Kit
New
Pancreatic Elastase ELISA Kit
Pancreatic Elastase ELISA
New
6-Channel Viscoelastometry Analyzer
ClotPro

Print article

Channels

Hematology

view channel
Image: Atellica Solution (Photo courtesy of Siemens Healthineers)

Siemens Introduces New Intelligent, Integrated IVD Solutions Virtually at EUROMEDLAB 2021

Siemens Healthineers (Erlangen, Germany) introduced new intelligent, integrated IVD solutions virtually at the XXIV IFCCEFLM European Congress of Clinical Chemistry and Laboratory Medicine (EuroMedLab... Read more

Immunology

view channel
Image: The Luminex 200 Instrument System sets the standard for multiplexing, providing the ability to perform up to 100 different tests in a single reaction volume on a flow cytometry-based platform (Photo courtesy of Luminex Corp)

Inflammatory Cytokines Measured in Infants Born to Preterm Preeclamptic Mothers

Preeclampsia is both a vascular and inflammatory disorder. The pathophysiology of preeclampsia is complex and rooted in the interplay between maternal and placental factors with the key characteristics... Read more

Microbiology

view channel
Image: The sciREADER CL2 enables high quality digital colorimetric imaging of various support formats (Photo courtesy of SCIENION)

Multiplex Immunoassay Developed for Confirmation and Typing of HTLV Infections

Human T-Cell Lymphotropic Viruses (HTLV) type 1 and type 2 account for an estimated five to 10 million infections worldwide and are transmitted through breast feeding, sexual contacts and contaminated... Read more

Pathology

view channel
Image: The Ventana BenchMark Ultra autostainer is for cancer diagnostics with automation and the test menu include IHC, ISH, and FITC tests (Photo courtesy of Ventana Medical System)

Specific Biomarker Investigated for Triple-Negative Breast Cancer Diagnosis

Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression and comprises a heterogeneous... Read more

Technology

view channel
Image: PKeye Workflow Monitor System (Photo courtesy of PerkinElmer, Inc.)

PerkinElmer’s New Cloud-Based Platform Enables Laboratory Personnel to Remotely Manage Its Instruments in Real-Time

PerkinElmer, Inc. (Waltham, MA; USA) has launched its PKeye Workflow Monitor, a cloud-based platform enabling laboratory personnel to remotely manage and monitor their PerkinElmer instruments and workflows... Read more

Industry

view channel
Illustration

Global Lateral Flow Assay Market to Reach Nearly USD 6.5 Billion by 2031 Due to Surge in Demand for Rapid POC Testing

The global lateral flow assay market is projected to grow at a CAGR of around 5% from USD 3.7 billion in 2020 to over USD 6.4 billion by 2031, driven by the growing adoption of home-based lateral flow... Read more
Copyright © 2000-2021 Globetech Media. All rights reserved.