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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
The treatment-naive microbiome in new-onset Crohn's disease.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.
The mutational constraint spectrum quantified from variation in 141,456 humans
A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
It is shown that SCFA–GPR43 interactions profoundly affect inflammatory responses, and GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways, and the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis are provided.
Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis
It is demonstrated that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium, and these findings suggest thatAutophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
An analysis of single-cell transcriptomics datasets from different tissues shows that ACE2 and TMPRSS2 are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of ACE2 is associated with genes involved in innate immunity.
Rational design of highly active sgRNAs for CRISPR-Cas9–mediated gene inactivation
An online tool for the design of highly active sgRNAs for any gene of interest is provided, including a further optimization of the protospacer-adjacent motif (PAM) of Streptococcus pyogenes Cas9.