Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism.
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| http://dx.doi.org/10.1038/hgv.2016.20 | DOI Listing |
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Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients.
Am J Respir Crit Care Med
May 2023
Marsico Lung Institute/UNC CF Research Center, School of Medicine.
Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance.
View Article and Find Full Text PDFCoordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region.
J Cell Mol Med
November 2019
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
E74-like factor 5 (ELF5) and ETS-homologous factor (EHF) are epithelial selective ETS family transcription factors (TFs) encoded by genes at chr11p13, a region associated with cystic fibrosis (CF) lung disease severity. EHF controls many key processes in lung epithelial function so its regulatory mechanisms are important. Using CRISPR/Cas9 technology, we removed three key cis-regulatory elements (CREs) from the chr11p13 region and also activated multiple open chromatin sites with CRISPRa in airway epithelial cells.
View Article and Find Full Text PDFNovel variation at chr11p13 associated with cystic fibrosis lung disease severity.
Hum Genome Var
July 2016
Marsico Lung Institute, CF/Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism.
View Article and Find Full Text PDFGenome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
Nat Genet
June 2011
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Article Synopsis
- A combined genome-wide association and linkage study was conducted to explore genetic factors influencing the severity of lung disease in cystic fibrosis patients, specifically focusing on those with the p.Phe508del mutation.
- Researchers found a strong genetic association near the EHF and APIP genes on chromosome 11 which was consistent in different study groups, with a highly significant P value (P = 1.49 × 10(-9)) when combining results from multiple studies.
- Additionally, they identified a significant quantitative trait locus on chromosome 20 (log(10) odds = 5.03) from sibling pair analysis, providing insights into the genetic mechanisms of cystic fibrosis and potential new targets for treatment.
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