Identification of Differentially Expressed Genes in Mouse Muscle Affected by Dysferlinopathy Using RNA-sequencing Data

Abstract

Dysferlinopathy is a rare form of muscular dystrophy defined by loss of function mutations in the gene DYSF, which codes for the membrane repair protein dysferlin. Loss of dysferlin function leads to natural damage from muscle contraction not being repaired, resulting in cell death and dystrophy of the muscle. Some muscle types are affected more severely by dysferlinopathy than others. A bioinformatics study was performed to determine differential expression of genes using wild type Mus musculus RNA, with a goal of discovering genes with a possible link to the severity of dysferlinopathy in different muscle types. Six wild type Mus musculus muscle tissues were compared (namely quadriceps, tibialis anterior, gastrocnemius, soleus, masseter, and diaphragm). Next generation sequencing software was used to quantify differential expression, and an analysis was performed on the data in Microsoft Excel. Gene Ontology software was also used to link genes of interest with biological pathways, and vice versa. Results of the study found that genes associated with membrane repair proteins are differentially expressed among different muscle types, which may contribute to the difference in severity of dysferlinopathy seen. It was also found that Caveolin-3, a gene associated with membrane repair, had significantly lower expression in muscle types with higher severity of muscular dystrophy, meaning that Cav-3 could play an important role in the severity of dysferlinopathy among different muscle types.

Sara Rogers | Biology and Chemistry | Faculty Sponsor Eric Williams