Publications by authors named "M E Knowles"
Several studies have now described instances where G-rich sequences in promoters and enhancers regulate gene expression through forming G-quadruplex (G4) structures. Relatedly, our group recently identified 301 long genomic stretches significantly enriched for minimal G4 motifs (LG4s) in humans and found the majority of these overlap annotated enhancers, and furthermore, that the promoters regulated by these LG4 enhancers are similarly enriched with G4-capable sequences. While the generally accepted model for enhancer:promoter specificity maintains that interactions are dictated by enhancer- and promoter-bound transcriptional activator proteins, the current study tested an alternative hypothesis: that LG4 enhancers interact with cognate promoters via a direct G4:G4 DNA-based mechanism.
View Article and Find Full Text PDFArticle Synopsis
- - A study evaluated the management of primary ciliary dyskinesia (PCD) in pediatric participants using a multicenter, observational approach, collecting data on therapy types and their annual usage.
- - Over 137 participants were monitored for 13 years, finding that nearly all received antibiotics, with a significant number using cephalosporins and chronic azithromycin, and older patients tended to utilize more therapies.
- - Results indicated that therapy usage varies significantly, often correlating with age and specific types of ciliary defects, highlighting the need for more disease-specific research to better understand the effectiveness of these treatments.
Article Synopsis
- PCD (Primary Ciliary Dyskinesia) and CF (Cystic Fibrosis) are both genetic diseases that affect how the lungs work and cause issues from a young age, but PCD is thought to be milder, even though evidence is limited.
- The study wanted to see how children with PCD compare to those with CF in terms of health over time, especially focusing on children with certain severe forms of PCD.
- They found that kids with PCD and the severe type had lower lung function than kids with CF, but their nutrition was similar, with more CF kids getting sick from bacteria in their lungs than PCD kids.
Variation in the non-coding genome represents an understudied mechanism of disease and it remains challenging to predict if single nucleotide variants, small insertions and deletions, or structural variants in non-coding genomic regions will be detrimental. Our approach using complementary RNA-seq and targeted long-read DNA sequencing can prioritize identification of non-coding variants that lead to disease via alteration of gene splicing or expression. We have identified a patient with primary ciliary dyskinesia with a pathogenic coding variant on one allele of the SPAG1 gene, while the second allele appears normal by whole exome sequencing despite an autosomal recessive inheritance pattern.
View Article and Find Full Text PDFTo identify modifier loci underlying variation in body mass index (BMI) in persons with cystic fibrosis (pwCF), we performed a genome-wide association study (GWAS). Utilizing longitudinal height and weight data, along with demographic information and covariates from 4,393 pwCF, we calculated AvgBMIz representing the average of per-quarter BMI Z scores. The GWAS incorporated 9.
View Article and Find Full Text PDF