Glaucoma Genetics: Where are we?
Subhabrata Chakrabarti, Hyderabad, India
Preamble: The glaucoma’s comprise a chronic and progressive group of hete-rogeneous optic neuropathies along with visual field defects.1 Raised intraocular pressure (IOP) may confer a significant risk to glaucoma.2 The underlying eti-ology is complex in nature and the molecular mechanisms are still unclear.3 Several risk factors such as age, gender, family history of the disease, systemic conditions and ethnicity have been sug-gested that enhances the susceptibility to glaucoma in varying degrees across populations.4-6 The mode of inheritance in adult-onset primary open angle (POAG) and primary angle-closure glaucoma’s (PACG) are complex in nature. This has been a major impediment in identifying large affected families for gene mapping by conventional linkage analysis.7 However, the hereditary component in juvenile-onset POAG facilitated the mapping of some candidate loci.8
Congenital and developmental glaucomas largely follow a Mendelian pattern with autosomal dominant and autosomal recessive modes of inheritance. Thus, co-segregation of candidate gene mutations among the affected subjects in such families could be thoroughly deciphered.9-11
A major impediment in understanding the genetics of glaucoma has been the lack of identification of all the genes involved at various stages of glaucoma pathophysiology. This has restricted the under-standing of gene-gene interactions as well as genotype-phenotype correlation in glaucomatous conditions.
In the near future, WGA in primary glaucomas with densely linked SNPs covering the entire genome on high throughput micro array platforms would be the method of choice.21 Additionally, finding structural variations within the genome would help in the identification of specific mutations leading to these conditions. These analyses provide a better and faster means of mapping genes when performed in isolated and inbred populations that are restricted to admixture and gene flow from other populations. Moreover, the haplotypes in these populations are conserved and rarely differentiated by genetic recombinations. WGA facilitates a huge generation of genomic data that would lead to understanding their associations with specific phenotypic conditions, which may be potential risk factors for glaucoma susceptibility. Understanding the interaction of these variants in combination would provide further insight into glaucoma pathogenesis that would have implications for predictive testing in populations.
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