Genetic dissection of the Gpnmb network in the eye

Hong Lu, Xusheng Wang, Matthew Pullen, Huaijin Guan, Hui Chen, Shwetapadma Sahu, Bing Zhang, Hao Chen, Robert Williams, Eldon E. Geisert, Lu Lu, Monica Jablonski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose. To use a systematic genetics approach to investigate the regulation of Gpnmb, a gene that contributes to pigmentary dispersion syndrome (PDS) and pigmentary glaucoma (PG) in the DBA/2J (D2) mouse. Methods. Global patterns of gene expression were studied in whole eyes of a large family of BXD mouse strains (n = 67) generated by crossing the PDS- and PG-prone parent (DBA/2J) with a resistant strain (C57BL/6J). Quantitative trait locus (eQTL) mapping methods and gene set analysis were used to evaluate Gpnmb coexpression networks in wild-type and mutant cohorts. Results. The level of Gpnmb expression was associated with a highly significant cis-eQTL at the location of the gene itself. This autocontrol of Gpnmb is likely to be a direct consequence of the known premature stop codon in exon 4. Both gene ontology and coexpression network analyses demonstrated that the mutation in Gpnmb radically modified the set of genes with which Gpnmb expression is correlated. The covariates of wild-type Gpnmb are involved in biological processes including melanin synthesis and cell migration, whereas the covariates of mutant Gpnmb are involved in the biological processes of posttranslational modification, stress activation, and sensory processing. Conclusions. These results demonstrated that a systematic genetics approach provides a powerful tool for constructing coexpression networks that define the biological process categories within which similarly regulated genes function. The authors showed that the R150X mutation in Gpnmb dramatically modified its list of genetic covariates, which may explain the associated ocular pathology.

Original languageEnglish (US)
Pages (from-to)4132-4142
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number7
DOIs
StatePublished - Jun 1 2011

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Biological Phenomena
Dissection
Open Angle Glaucoma
Genes
Inbred DBA Mouse
Mutation
Gene Ontology
Nonsense Codon
Chromosome Mapping
Quantitative Trait Loci
Melanins
Post Translational Protein Processing
Cell Movement
Exons
Pathology
Gene Expression

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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Genetic dissection of the Gpnmb network in the eye. / Lu, Hong; Wang, Xusheng; Pullen, Matthew; Guan, Huaijin; Chen, Hui; Sahu, Shwetapadma; Zhang, Bing; Chen, Hao; Williams, Robert; Geisert, Eldon E.; Lu, Lu; Jablonski, Monica.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 7, 01.06.2011, p. 4132-4142.

Research output: Contribution to journalArticle

Lu, H, Wang, X, Pullen, M, Guan, H, Chen, H, Sahu, S, Zhang, B, Chen, H, Williams, R, Geisert, EE, Lu, L & Jablonski, M 2011, 'Genetic dissection of the Gpnmb network in the eye', Investigative Ophthalmology and Visual Science, vol. 52, no. 7, pp. 4132-4142. https://doi.org/10.1167/iovs.10-6493
Lu, Hong ; Wang, Xusheng ; Pullen, Matthew ; Guan, Huaijin ; Chen, Hui ; Sahu, Shwetapadma ; Zhang, Bing ; Chen, Hao ; Williams, Robert ; Geisert, Eldon E. ; Lu, Lu ; Jablonski, Monica. / Genetic dissection of the Gpnmb network in the eye. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 7. pp. 4132-4142.
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AU - Chen, Hao

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