A Study of Cis-Regulatory Sequences Of Wnt1 in the Disease Osteogenesis Imperfecta

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2021-05

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Abstract

Wnt1 is known to be mutated in the inherited cases of the disease Osteogenesis Imperfecta, a bone genetic disorder also known as the brittle bone disease. The canonical Wnt signaling pathway has a known role in bone homeostasis and development and studies have shown that wnt1, an evolutionarily conserved member of the Wnt signaling pathway, is particularly important for the Wnt canonical pathway in osteoblast differentiation. This suggests a potential role of wnt1 in bone homeostasis. Understanding the regulation of wnt1 expression by cis-regulatory elements during development is important to understand the role it plays in bone development and homeostasis. This project uses ATAC seq (Assay for Transposase-Accessible Chromatin) datasets available to the public to study regions within and surrounding the wnt1 gene to find open chromatin regions, as this is associated with enhancer activity. The enhancers that are shown to be active are studied closely using the ENCODE project to obtain information on the expression profiles of the enhancers and the tissue in which they may be active. The activity of the enhancers was compared in tissues where wnt1-signaling is known to be important: hindbrain tissue, adipose tissue, and bone marrow macrophage and two enhancers with the highest activity were identified. By knowing these cis-regulatory sequences of wnt1, now it could be easier to possibly use wnt1 expression as a therapeutic target in the disease Osteogenesis Imperfecta.

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Keywords

Osteogenesis Imperfecta, Bone diseases

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