![]() Each recombinant inbred strain has its advantages. Table 1 lists the attributes of each strain and the strain set–specific tools available for data analysis. These recombinant inbred strains have been used in studies of the visual system, focusing mainly on the retina. In addition, the CC is used to create the mouse diversity outbred strains. Progress in systems genetics was driven by the development of greatly expanded families of fully isogenic replicable cohorts, in particular the BXD strain set (parental strains, the C57BL/6J mouse and the DBA/2J mouse, Figure 1), the AXB/BXA strain set (parental strains, the AJ mouse and the C57BL/6J mouse), and the collaborative cross (CC,). When this omics combination is coupled with classic genetics (i.e., genetically diverse populations), it is referred to as systems genetics essentially systems biology but in a rich genetics and omics context. For the first time, we can, in principle, combine a systems approach across the entire visual system (from the cornea to the cortex to visually guided behavior) using global omics and genetic methods, including epigenomic, proteomic, metabolomic, and lipidomic methods. We can then move on to the more important stage of research to probe linked molecular and cellular networks associated with variation in the eye and visual system structure, function, disease, and treatment. A second major advance is our ability to systematically define and validate causal gene variants with increasing precision, power, and efficiency. In the case of isogenic cohorts of mice and rats, the analysis of single genomes can be extended to multiple time points during development, aging, and in the progression of blinding diseases, making it possible to study gene-by-environmental and gene-by-treatment effects in ways that have high translational relevance to human clinical disease. We are now at the point that is practical to consider in-depth analyses across large cohorts of human populations and rodent models. Over this same period, the costs of generating high-quality phenome and genome data have been decreased, and data quality and throughput have improved greatly. Since the first wave of whole genome sequencing in the early 2000s, teams of investigators have developed open genetic, genomic, and transcriptomic resources to study the eye, visual system, and blinding diseases. The role of three of these gene variants in glaucoma is discussed, along with the pathways activated in the disease process. The power of this experimental approach to precision medicine is highlighted by recent studies that defined cadherin 11 ( Cdh11) and a calcium channel ( Cacna2d1) as genes modulating IOP, Pou6f2 as a genetic link between CCT and retinal ganglion cell (RGC) death, and Aldh7a1 as a gene that modulates the susceptibility of RGCs to death after elevated IOP. The BXD family was exploited to define key gene variants and then establish linkage to glaucoma in human cohorts. Recent studies focused on retinal ganglion cells and glaucoma risk factors, including intraocular pressure (IOP), central corneal thickness (CCT), and susceptibility of cellular stress. Over the past 16 years, our group has integrated powerful murine resources and web-accessible tools to identify networks modulating visual system traits-from photoreceptors to the visual cortex. ![]() ![]() We illustrate the growing power of the BXD family of mice (recombinant inbred strains from a cross of C57BL/6J and DBA/2J mice) and companion bioinformatic tools to study complex genome-phenome relations related to glaucoma.
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