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Author Notes:

Correspondence to: Lu Lu, 71 S. Manassas St, Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163; Phone: (901) 448-7557; FAX: (901) 448-3500; email: lulu@uthsc.edu

Subjects:

Research Funding:

This work was supported by NIH Grant R01EY021200 (LL, PI), NIH grant R01EY017841 (EEG, PI), NIH grants R01EY022694 and R01EY026629 (WZ, PI), DoD Grant W81XWH-12–1-0255 (EEG, PI), Research to Prevent Blindness Stein Innovation Award (Robert Williams, PI), and Vision Core Grant P30EY006360 (P. Michael Iuvone, PI).

This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.

We thank Dr. Robert Williams for his financial and bioinformatics support for this study.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Ophthalmology
  • USHER-SYNDROME 1B
  • FAMILIAL EXUDATIVE VITREORETINOPATHY
  • MULTIPLE SULFATASE DEFICIENCY
  • SYNDROMIC HEARING-LOSS
  • BARDET-BIEDL-SYNDROME
  • MYOSIN VIIA GENE
  • SYNDROME TYPE-I
  • EXONUCLEASE TREX1
  • MOUSE RETINA
  • DBA/2J MICE

The genetic dissection of Myo7a gene expression in the retinas of BXD mice

Journal Title:

Molecular Vision

Volume:

Volume 24

Publisher:

, Pages 115-126

Type of Work:

Article | Final Publisher PDF

Abstract:

Usher syndrome (US) is characterized by a loss of vision due to retinitis pigmentosa (RP) and deafness. US has three clinical subtypes, but even within each subtype, the severity varies. Myosin VIIA, coded by Myo7a, has been identified as one of the causal genes of US. This study aims to identify pathways and other genes through which Myo7a interacts to affect the presentation of US symptoms. Methods: In this study, we used the retinal tissue of BXD recombinant inbred (RI) mice to examine the expression of Myo7a and perform genetic mapping. Expression quantitative trait locus (eQTL), single nucleotide polymorphism (SNP), and gene correlation analysis were performed using GeneNetwork. Gene set enrichment analysis was performed using WebGestalt, and gene network construction was performed using the Gene Cohesion Analysis Tool. Results: We found Myo7a to be cis-regulated, with varied levels of expression across BXD strains. Here, we propose a genetic network with 40 genes whose expression is highly correlated with Myo7a. Among these genes, six have been linked to retinal diseases, three to deafness, and five share a transcription factor with Myo7a. Gene ontology and pathway analysis revealed a strong connection among ion channel activity, Myo7a, and US. Conclusions: Although Myo7a is a causal gene of US type I, this gene works with many other genes and pathways to affect the severity of US. Many of the genes found in the genetic network, pathways, and gene ontology categories of Myo7a are related to either deafness or blindness. Further investigation is needed to examine the specific relationships between these genes, which may assist in the treatment of US.

Copyright information:

© 2018 Molecular Vision.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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