Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Point and Frameshift Mutations01:30

Point and Frameshift Mutations

780
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
780
Genetic Screens02:46

Genetic Screens

5.6K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.6K
Mutations01:39

Mutations

94.3K
Overview
94.3K
Mutations01:35

Mutations

42.6K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
42.6K
RNA Editing02:23

RNA Editing

9.7K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.7K
Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

2.0K
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
2.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.

Circulation·2026
Same author

Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects.

Nature communications·2026
Same author

Publisher Correction: Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting.

Nature genetics·2026
Same author

Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting.

Nature genetics·2026
Same author

Experimental assessment of AI-based interactome mapping.

Nature communications·2026
Same author

A scalable approach to resolving variants of uncertain significance.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: Jan 9, 2026

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants
06:35

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

2.3K

Systematic and proactive evaluation of AIRE missense variant effects.

Anna Axakova1,2,3, Amund Holte Berger4, Warren van Loggerenberg1,2,3,5

  • 1Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.

Biorxiv : the Preprint Server for Biology
|December 3, 2025
PubMed
Summary

This study created an AIRE variant effect map to proactively assess gene function. This resource aids in the rapid and definitive diagnosis of Autoimmune Polyendocrine Syndrome Type 1 (APS-1).

More Related Videos

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.3K
Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

5.9K

Related Experiment Videos

Last Updated: Jan 9, 2026

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants
06:35

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

2.3K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.3K
Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

5.9K

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Pathogenic variants in the Autoimmune Regulator (AIRE) gene cause Autoimmune Polyendocrine Syndrome Type 1 (APS-1), a rare primary immunodeficiency.
  • AIRE is crucial for preventing autoimmunity by eliminating self-reactive T cells.
  • Many AIRE variants are classified as variants of uncertain significance (VUS), hindering diagnosis.

Purpose of the Study:

  • To proactively assess the functional impact of AIRE missense variants.
  • To create a comprehensive AIRE variant effect map for improved genetic diagnosis.
  • To provide evidence for classifying VUS and enhancing APS-1 diagnosis.

Main Methods:

  • Utilized an insulin promoter-driven reporter system to functionally assay 9790 AIRE missense variants.
  • Generated an AIRE variant effect map.
  • Correlated variant data with an international APS-1 cohort and UK BioBank data.

Main Results:

  • The AIRE variant effect map validated and extended biochemical knowledge.
  • The map provided proactive evidence for 70% of previously reported VUS.
  • Quantitative genotype-phenotype correlations were identified, enabling classification for 32% of VUS.

Conclusions:

  • The proactive AIRE variant effect map offers a valuable resource for improving patient outcomes.
  • This resource facilitates more rapid and definitive diagnosis of APS-1.
  • The study enhances understanding of AIRE variant pathogenicity and its clinical implications.