Related Experiment Video

Updated: Jun 5, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Identification and characterization of a loss-of-function human MPYS variant

L Jin1, L-G Xu, I V Yang

  • 1Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO 80206-2762, USA.

Genes and Immunity
|January 21, 2011
PubMed

Insights

A newly identified MPYS gene variant, the HAQ haplotype, significantly impairs interferon-beta production, potentially increasing susceptibility to infections and reducing vaccine efficacy in approximately 3% of Americans.

Area of Science:

  • Immunology
  • Genetics

Background:

  • MPYS (also known as STING and MITA) is crucial for innate immunity, stimulating interferon-beta (IFNβ) production.
  • MPYS plays a role in host defense against pathogens and enhances DNA vaccine adjuvant activity.

Purpose of the Study:

  • To identify and characterize a novel human MPYS haplotype.
  • To investigate the functional consequences of this haplotype on IFNβ production and host defense.

Main Methods:

  • Identification of a distinct human MPYS haplotype (R71H-G230A-R293Q, termed HAQ).
  • Genotyping in two cohorts (1,074 individuals) to estimate HAQ haplotype frequency.
  • Functional assays using fibroblasts and macrophages to assess IFNβ production and response to Listeria monocytogenes.

Main Results:

  • Approximately 3% of Americans are homozygous for the HAQ MPYS haplotype.
  • HAQ MPYS demonstrates a >90% loss in IFNβ stimulatory capacity.
  • Cells expressing HAQ are impaired in IFNβ production following Listeria monocytogenes infection.
  • The R71H and R293Q SNPs are primarily responsible for the reduced IFNβ activity.

Conclusions:

  • The HAQ MPYS haplotype significantly compromises the innate immune response by impairing IFNβ production.
  • Individuals homozygous for HAQ may face increased susceptibility to viral infections.
  • The HAQ haplotype might lead to a diminished response to DNA vaccines.

More Related Videos

Functional Characterization of Endogenously Expressed Human RYR1 Variants07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...