Abstract
The goal of this research is to computationally identify candidate modifiers for retinitis pigmentosa (RP), a group of rare genetic disorders that trigger the cellular degeneration of retinal tissue. RP being subject to phenotypic variation complicates diagnosis and treatment of the disease. In a previous study, modifiers of RP were identified by an association between genetic variation in the DNA sequence and variation in eye size in a well-characterized Drosophila model of RP. This study will instead focus on RNA expression data to identify candidate modifier genes whose expression is correlated with phenotypic variation in eye size. The proposed approach uses the K-Means algorithm to cluster 171 Drosophila strains based on their expression profiles for 18,140 genes in adult females. This algorithm is designed to investigate the correlation between Drosophila eye size and genetic expression and gather suspect genes from clusters with abnormally large or small eyes. The clustering algorithm was implemented using the R scripting language and successfully identified 10 suspected candidate modifiers for RP. This analysis was followed by a validation study that tested seven candidate modifiers and found that the loss of five of them significantly altered the degeneration phenotype and thus can be labeled as a bona fide modifier of disease.
Highlights
Retinitis pigmentosa (RP) is a degenerative disease resulting in the death of cells in the retina—the light-sensitive tissue that lines the back of the eye [1]
The objective of the research reported in this paper is to computationally identify candidate modifiers for RP using the Drosophila Genetic Reference Panel (DGRP) expression data
The clustering algorithm used in this study was able to identify 89 statistically significant genes with a notable correlation between mean eye size and genetic expression
Summary
Retinitis pigmentosa (RP) is a degenerative disease resulting in the death of cells in the retina—the light-sensitive tissue that lines the back of the eye [1]. 15–35% of RP cases are inherited in an autosomal-dominant (AD) manner, meaning that a single copy of the causative mutation triggers the disease [2]. Approximately 25–30% of the AD-inherited RP cases are found in the gene rhodopsin (RHO) [3]. These mutations commonly lead to misfiling proteins, endoplasmic reticulum stress and apoptosis [4]. Chow et al analyzed the genetic factors that influence RP progression using the Drosophila Genetic Reference Panel (DGRP) [5]. The DGRP is a collection of ~200 inbred
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.