Genomic Locus Modulating IOP in the BXD RI Mouse Strains

G3 : Genes - Genomes - Genetics
Rebecca KingEldon E Geisert

Abstract

Intraocular pressure (IOP) is the primary risk factor for developing glaucoma, yet little is known about the contribution of genomic background to IOP regulation. The present study leverages an array of systems genetics tools to study genomic factors modulating normal IOP in the mouse. The BXD recombinant inbred (RI) strain set was used to identify genomic loci modulating IOP. We measured the IOP in a total of 506 eyes from 38 different strains. Strain averages were subjected to conventional quantitative trait analysis by means of composite interval mapping. Candidate genes were defined, and immunohistochemistry and quantitative PCR (qPCR) were used for validation. Of the 38 BXD strains examined the mean IOP ranged from a low of 13.2mmHg to a high of 17.1mmHg. The means for each strain were used to calculate a genome wide interval map. One significant quantitative trait locus (QTL) was found on Chr.8 (96 to 103 Mb). Within this 7 Mb region only 4 annotated genes were found: Gm15679, Cdh8, Cdh11 and Gm8730 Only two genes (Cdh8 and Cdh11) were candidates for modulating IOP based on the presence of non-synonymous SNPs. Further examination using SIFT (Sorting Intolerant From Tolerant) analysis revealed that the SNPs in Cdh8 (Cadher...Continue Reading

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Citations

Mar 17, 2020·Frontiers in Genetics·Andrew B StiemkeMonica M Jablonski
Jul 13, 2021·Translational Vision Science & Technology·Nan ZhangJohn M Nickerson

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Methods Mentioned

BETA
PCR
Assay
RNA-seq
RNA Seq

Software Mentioned

EZ
WebQTL
GeneNetwork
- C1

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