Related Experiment Video
Updated: Jul 2, 2026
07:04
Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
Gene modifiers in cystic fibrosis.
Frank J Accurso1, Marci K Sontag
1Department of Pediatrics, Mike McMorris Cystic Fibrosis Care and Research Center, Children's Hospital, University of Colorado, Aurora, Colorado 80045, USA. FAccurso@tchden.org
The Journal of Clinical Investigation
|February 23, 2008
Summary
This study shows that mannose-binding lectin 2 and TGF-beta1 genes impact lung disease in pediatric cystic fibrosis (CF) patients. Gene interactions highlight the complexity of CF lung disease, supporting prospective genetic analysis in trials and newborn screening.
Area of Science:
- Genetics
- Pulmonology
- Immunology
Background:
- Previous cystic fibrosis (CF) modifier gene studies used small populations, yielding inconsistent results.
- Understanding genetic modifiers is crucial for predicting CF lung disease severity and progression.
Discussion:
- Dorfman et al. conducted a large, population-based study on CF modifier genes.
- The study focused on mannose-binding lectin 2 (MBL2) and TGF-beta1, previously implicated in CF.
- Gene-gene interactions between MBL2 and TGF-beta1 were identified, adding complexity to CF lung disease.
Key Insights:
- Two specific genes, MBL2 and TGF-beta1, significantly influence pulmonary outcomes in pediatric CF patients.
- A significant gene-gene interaction was observed between MBL2 and TGF-beta1.
- These findings emphasize the intricate genetic landscape of CF lung disease.
Outlook:
- Further research into MBL2, TGF-beta1, and their associated signaling pathways in CF is warranted.
- Prospective collection of known CF modifier gene genotypes in clinical trials and newborn screening studies is recommended.
- Longitudinal studies are essential to precisely define the impact of genetic modifiers on CF progression.
Related Concept Videos
01:39Mutations
Overview
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
01:35Mutations
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...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:24Cystic Fibrosis: Management
Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic sinusitis...
Sinus disease and chronic sinusitis...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...