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Genomic Locus Modulating IOP in the BXD RI Mouse Strains
Rebecca King1, Ying Li1, Jiaxing Wang1,2
1Department of Ophthalmology, Emory University, Atlanta, Georgia 30322.
G3 (Bethesda, Md.)
|March 3, 2018
Summary
Genomic background influences intraocular pressure (IOP). Researchers identified a significant quantitative trait locus (QTL) on mouse chromosome 8, pinpointing Cadherin 11 (CDH11) as a key gene regulating IOP.
Area of Science:
- Genetics
- Ophthalmology
- Systems Biology
Background:
- Intraocular pressure (IOP) is a primary risk factor for glaucoma.
- The genetic contribution to normal IOP regulation is not well understood.
- Systems genetics approaches can identify genomic factors influencing complex traits.
Purpose of the Study:
- To identify genomic loci and candidate genes that modulate normal intraocular pressure (IOP) in mice.
- To investigate the role of specific genes within a significant quantitative trait locus (QTL).
Main Methods:
- Utilized the BXD recombinant inbred (RI) mouse strain set for quantitative trait analysis.
- Measured IOP in 506 eyes across 38 different mouse strains.
- Employed composite interval mapping, SIFT analysis, quantitative PCR, and immunohistochemistry for gene validation.
Main Results:
- A significant QTL for IOP was identified on mouse chromosome 8 (96-103 Mb).
- Four annotated genes were located within this QTL, with Cdh8 and Cdh11 identified as candidates.
- Cadherin 11 (CDH11) harbored non-tolerated single nucleotide polymorphisms (SNPs) and was expressed in the trabecular meshwork.
Conclusions:
- One significant QTL on chromosome 8 regulates IOP in the BXD RI strain set.
- Cadherin 11 (CDH11) is a strong candidate gene for modulating IOP due to its genetic variation and expression in ocular tissues.
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