comprehensive analysis of copy number variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration基因拷贝数变异的综合分析1到10号染色体位点与年龄相关黄斑变性.pdf

Comprehensive Analysis of Copy Number Variation of Genes at Chromosome 1 and 10 Loci Associated with Late Age Related Macular Degeneration 1,2 2 1 1 1 Stuart Cantsilieris , Stefan J. White , Andrea J. Richardson , Robyn H. Guymer , Paul N. Baird * 1 Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia, 2 Centre for Reproduction and Development, Monash Institute of Medical Research, Melbourne, Victoria, Australia Abstract Copy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both risk and protection in AMD, the role of CNVs has remained largely unexplored. We analyzed the two major AMD risk-associated regions on chromosome 1q32 and 10q26 for CNVs using Multiplex Ligation-dependant Probe Amplification. The analysis targeted nine genes in these two key regions, including the Complement Factor H (CFH) gene, the 5 CFH-related (CFHR) genes representing a known copy number ‘‘hotspot’’, the F13B gene as well as the ARMS2 and HTRA1 genes in 387 cases of late AMD and 327 controls. No copy number variation was detected at the ARMS2 and HTRA1 genes in the chromosome 10 region, nor for the CFH and F13B genes at the chromosome 1 region. However, significant association was identified for the CFHR3-1 deletion in AMD cases (p = 2.38 610212) OR = 0.31, CI-0.95 (0.23–0.44), for both neovascular disease (nAMD) (p = 8.3 61029) OR = 0.36 CI-0.95 (0.25– 0.52) and g