Identifying the link between non-coding regulatory RNAs and phenotypic severity in a zebrafish model of gmppb dystroglycanopathy
Grace Smith
Erin Bailey
Michelle Goody
Clarissa Henry
Benjamin King
10.6084/m9.figshare.12150333.v1
https://tagc2020.figshare.com/articles/poster/Identifying_the_link_between_non-coding_regulatory_RNAs_and_phenotypic_severity_in_a_zebrafish_model_of_gmppb_dystroglycanopathy/12150333
<p>Muscular
Dystrophy (MD) is characterized by varying severity and time-of-onset by
individuals afflicted with the same forms of MD, a phenomenon that is not well
understood. Mutations in gmppb, an
enzyme that glycosylated dystroglycan, cause
dystroglycanopathic MD1.
Like human patients, gmppb
mutant zebrafish present both mild and severe phenotypes. In order to
understand the molecular mechanisms involved, we performed high-throughput RNA
Sequencing (RNA-Seq) and small RNA Sequencing at 4 and 7
days-post-fertilization (dpf) in mild and severe gmppb
mutants and controls. We hypothesize that variable phenotypes in gmppb
mutants are due to differences in gene regulation; therefore, we identified
differentially expressed (DE) long non-coding RNAs (lncRNAs) and microRNAs
(miRNAs) - both potent genetic regulators. In the 4dpf severe mutants, we
identified DE “MD-relevant” Ensembl-annotated genes that were predicted targets
of DE miRNAs – identifying 55 of these interactions. We utilized a novel method
of visualizing gene expression networks by generating co-expression miRNA
networks and subsequently removing miRNA nodes to identify miRNAs that maintain
network stability. We identified 95 potential lncRNAs for further analysis. By
integrating analyses of both coding and non-coding
genes, we hope to better understand the molecular mechanisms of
dystroglycanopathy, highlighting potential phenotypic modulators.</p>
2020-04-20 22:03:26
Long non-coding RNAs
microRNAs
Muscular Dystrophy
Bioinformatics
Epigenetics (incl. Genome Methylation and Epigenomics)