Four Novel Gene Polymorphisms Cause Nuclear Age Related Cataract in Chinese People 

Background: More information on genetic variation can be obtained by exon sequencing for the diagnosis of nuclear age-related cataract (NARC). Methods: In our present study, genomes of 12 DNA samples were sequenced. The average effective depth was 10× when using Illumina sequencing. After conducting whole-exon sequencing, we further performed depth analysis and spectrum analysis to determine the gene polymorphism sites closely associated with NARC. Results: In genes showing single nucleotide polymorphism (SNP), there were 18,699 synonymous mutations and 17,975 missense mutations in the coding region. A total of 4,944 insertions and deletions (indels) were found. Among them, 1329 indels exhibited polymorphism and were further analyzed. Whole-exon sequencing previously showed polymorphism associated with ARC and known pathways associated with protein synthesis and metabolism. Following depth analysis (GO and KEGG analysis), we identified 20 promising candidate genes that were closely related to NARC. We further performed spectrum analysis for 26 polymorphism sites and found that ZNF573 (rs3095726, SNP), ZNF862 (rs62621204, SNP), SYNE3 (rs76499929, indel), and GAS2L2 (rs78557458, SNP) had statistically significant relationship with NARC. The 3D protein structure showed obvious changes for ZNF573 (rs3095726, SNP) and GAS2L2 (rs78557458, SNP). Conclusions: Our findings provide the basis for further studies and discovery of key genes associated with NARC.