Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Determinants of Bacterial Pathogenicity and Virulence

Determinants of Bacterial Pathogenicity and Virulence

Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...

You might also read

Related Articles

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

Sort by

Same author

Soluble endoglin versus sFlt-1/PlGF ratio: detection of preeclampsia, HELLP syndrome, and FGR in a high-risk cohort.

Hypertension in pregnancy·2022

Same author

Autologous cell replacement: a noninvasive AI approach to clinical release testing.

The Journal of clinical investigation·2020

Same author

AUTOIMMUNE RETINOPATHY MIMICKING HERITABLE RETINAL DEGENERATION IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY.

Retinal cases & brief reports·2019

Same author

A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an <i>ELOVL4</i> mutation.

Neurology. Genetics·2019

Same author

Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration.

Proceedings of the National Academy of Sciences of the United States of America·2019

Same author

Scleral pits represent degeneration around the posterior ciliary arteries and are signs of disease severity in choroideremia.

Eye (London, England)·2019

Search research articles

Related Experiment Video

Updated: Jun 23, 2026

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

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

Published on: April 4, 2018

Predicting the pathogenicity of RPE65 mutations.

A R Philp¹, M Jin, S Li

¹Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

|May 12, 2009

Summary

An objective algorithm, the estimate of pathogenic probability (EPP), accurately distinguishes disease-causing mutations from benign variants. This tool shows high concordance with functional assays for RPE65 gene variations linked to Leber congenital amaurosis.

More Related Videos

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

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

Published on: January 16, 2019

Related Experiment Videos

Last Updated: Jun 23, 2026

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

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

Published on: April 4, 2018

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

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

Published on: January 16, 2019

Area of Science:

Genetics
Molecular Biology
Ophthalmology

Background:

Distinguishing pathogenic mutations from nonpathogenic polymorphisms is crucial for genetic diagnosis.
Leber congenital amaurosis (LCA) is a severe inherited retinal disease often caused by mutations in the RPE65 gene.

Purpose of the Study:

To develop and validate an objective algorithm, the estimate of pathogenic probability (EPP), for assessing the pathogenicity of missense variations.
To evaluate the EPP algorithm's accuracy using RPE65 gene variations in LCA patients.

Main Methods:

Developed an EPP algorithm incorporating variation prevalence, family segregation, and predicted protein structure effects.
Assessed eleven missense variations in the RPE65 gene using the EPP algorithm.
Validated EPP predictions through a cell-culture assay measuring RPE65-isomerase activity.

Main Results:

The EPP algorithm correctly identified eight disease-causing RPE65 variants with <6% wild-type isomerase activity.
The algorithm also identified three non-disease-causing variants with isomerase activities ranging from 68% to 127% of wild-type.
Complete concordance was observed between EPP predictions and functional assay results.

Conclusions:

The EPP algorithm accurately predicts the pathogenicity of missense variations in the RPE65 gene.
This objective algorithm shows potential utility for evaluating missense variations in other disease genes, especially when functional assays are unavailable.