Video Experimental Relacionado

Updated: May 23, 2026

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

ConPath 2.0: una estrategia de consenso optimizada para evaluar la potencial patogenicidad de las variantes de error

Giulio Poli¹, Salvatore Galati¹, Marco Macchia¹

¹Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Journal of molecular modeling

|August 20, 2025

Resumen

Desarrollamos una herramienta computacional, ConPath 2.0, para evaluar rápidamente el impacto de las variantes de la retinoide isomerasa humana 65 (hRPE65). Esta estrategia ayuda a reclasificar variantes inciertas y ayuda a las decisiones de terapia génica para trastornos de la retina.

Área de la Ciencia:

La genética
Oftalmología
Biología computacional

Sus antecedentes:

La isomerasa retinoide humana 65 (hRPE65) es crucial para el ciclo visual.
Las variantes de Missense en hRPE65 están asociadas con trastornos de la retina como la retinitis pigmentaria.
Muchas variantes de hRPE65 son de importancia incierta (VUS), lo que dificulta el diagnóstico y la selección de la terapia génica.

Objetivo del estudio:

Desarrollar una estrategia computacional para evaluar la patogenicidad de las variantes de hRPE65 de importancia incierta.
Reclasificar más de 200 hRPE65 VUS y apoyar la toma de decisiones clínicas para la terapia génica.

Principales métodos:

Optimizado el enfoque de ConPath mediante la expansión a 27 herramientas predictivas, incluidos los métodos basados en 3D.
Se ha refinado el marco estadístico para la selección de herramientas utilizando más de 70 métodos.
Se evaluó el rendimiento de la herramienta en variantes conocidas de hRPE65 y se aplicó el ConPath 2.0 mejorado a 210 VUS de ClinVar.

Principales resultados:

La estrategia mejorada ConPath 2.0 proporciona una evaluación rápida y confiable de hRPE65 VUS.
Se generaron información valiosa para apoyar la reclasificación de estas variantes.
Los hallazgos ayudan a los médicos a evaluar la idoneidad del paciente para la terapia génica dirigida a hRPE65.

Conclusiones:

La estrategia ConPath 2.0 aborda efectivamente el desafío de clasificar el VUS hRPE65.
Este enfoque computacional facilita el diagnóstico preciso y las estrategias de tratamiento personalizadas para los trastornos de la retina.
La mejora de la clasificación de variantes ayuda a avanzar en la terapia génica para las enfermedades hereditarias de la retina.

Palabras clave:

hRPE65 (en inglés)Las predicciones de la bioinformática ConPath también.Mutaciones de mal sentido Variante de importancia incierta

Más Videos Relacionados

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Identification and Classification of Position-specific GABA_A Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

Videos de Conceptos Relacionados

Comparing Copy Number Variations and SNPs

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

In vitro Mutagenesis

In vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

Genetic Screens

Genetic Screens

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 result in visible changes...

Single Nucleotide Polymorphisms-SNPs

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...

Principles of Pharmacogenetics: Types of Genetic Variants

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

Point and Frameshift Mutations

Point and Frameshift Mutations

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...