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Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

ABSTRACT: Inflammatory bowel disease (IBD) manifests as a complex disease resulting from gene-environment interactions or as a monogenic disease resulting from deleterious mutations. While monogenic IBD is predominantly pediatric, only one-quarter of complex IBD is pediatric. In this study, we were the first to systematically compare genetic architecture between monogenic and complex pediatric and adult IBD on genetic and molecular pathway levels. Genes reported as causal for monogenic pediatric IBD and related syndromes and as risk factors for pediatric and adult complex IBD were analyzed using CytoScape and ClueGO software tools to elucidate significantly enriched Gene Ontology (GO) terms. Despite the small overlap (seven genes) between monogenic IBD genes (85) and complex IBD loci (240), GO analysis revealed several enriched GO terms shared between subgroups (13.9%). Terms Th17 cell differentiation and Jak/STAT signaling were enriched in both monogenic and complex IBD subgroups. However, primary immunodeficiency and B-cell receptor signaling pathway were specifically enriched only for pediatric subgroups, confirming existing clinical observations and experimental evidence of primary immunodeficiency in pediatric IBD patients. In addition, comparative analysis identified patients below 6 years of age to significantly differ from complex pediatric and adult IBD and could be considered a separate entity.

SUBMITTER: Jezernik G

PROVIDER: S-EPMC7712254 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

Jezernik Gregor G Mičetić-Turk Dušanka D Potočnik Uroš U

Journal of personalized medicine 20201126 4

Inflammatory bowel disease (IBD) manifests as a complex disease resulting from gene-environment interactions or as a monogenic disease resulting from deleterious mutations. While monogenic IBD is predominantly pediatric, only one-quarter of complex IBD is pediatric. In this study, we were the first to systematically compare genetic architecture between monogenic and complex pediatric and adult IBD on genetic and molecular pathway levels. Genes reported as causal for monogenic pediatric IBD and r ...[more]

PMID: 33255894

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Project description:Background and aimsIn woody species, the juvenile period maintains the axillary meristems in a vegetative stage, unable to flower, for several years. However, in adult trees, some 1-year-old meristems flower whereas others remain vegetative to ensure a polycarpic growth habit. Both types of trees, therefore, have non-flowering meristems, and we hypothesize that the molecular mechanism regulating flower inhibition in juvenile trees is different from that in adult trees.MethodsIn adult Citrus trees, the main endogenous factor inhibiting flower induction is the growing fruit. Thus, we studied the expression of the main flowering time, identity and patterning genes of trees with heavy fruit load (not-flowering adult trees) compared to that of 6-month-old trees (not-flowering juvenile trees). Adult trees without fruits (flowering trees) were used as a control. Second, we studied the expression of the same genes in the meristems of 6-month, and 1-, 3-, 5- and 7-year-old juvenile trees compared to 10-year-old flowering trees.Key resultsThe axillary meristems of juvenile trees are unable to transcribe flowering time and patterning genes during the period of induction, although they are able to transcribe the FLOWERING LOCUS T citrus orthologue (CiFT2) in leaves. By contrast, meristems of not-flowering adult trees are able to transcribe the flowering network genes but fail to achieve the transcription threshold required to flower, due to CiFT2 repression by the fruit. Juvenile meristems progressively achieve gene expression, with age-dependent differences from 6 months to 7 years, FD-like and CsLFY being the last genes to be expressed.ConclusionsDuring the juvenile period the mechanism inhibiting flowering is determined in the immature bud, so that it progressively acquires flowering ability at the gene expression level of the flowering time programme, whereas in the adult tree it is determined in the leaf, where repression of CiFT2 gene expression occurs.

Dataset Information

Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

Publications

Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

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