Rydzanicz Malgorzata, Nath Swapan K, Sun Celi, Podfigurna-Musielak Monika, Frajdenberg Agata, Mrugacz Malgorzata, Winters Daniel, Ratnamala Uppala, Radhakrishna Uppala, Bejjani Bassem A, Gajecka Marzena
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Mol Vis. 2011;17:2028-39. Epub 2011 Jul 22.
Myopia is the most common human eye disorder with complex genetic and environmental causes. To date, several myopia loci have been identified in families of different geographic origin. However, no causative gene(s) have yet been identified. The aim of this study was the characterization of Polish families with high-grade myopia, including genetic analysis.
Forty-two multiplex Polish families with non-syndromic high-grade myopia participated in the study. All family members underwent detailed ophthalmic examination and high-grade myopia was defined as ≤-6.0 diopters (D) based on the spherical refractive error. A genome-wide single nucleotide polymorphism (SNP)-based high-density linkage scan was performed using Affymetrix Human SNP Array 6.0 on a selected family (HM-32) with multiple affected individuals.
Nonparametric linkage analysis identified three novel loci in family HM-32 at chromosome 7p22.1-7p21.1 ([NPL] 8.26; p=0.006), chromosome 7p12.3-7p11.2 ([NPL] 8.23; p=0.006), and chromosome 12p12.3-12p12.1 ([NPL] 8.02; p=0.006), respectively. The effect of linkage disequilibrium on linkage due to dense SNP map was addressed by systematically pruning SNPs from the linkage panel.
Haplotype analysis with informative crossovers in affected individuals defined a 12.2; 10.9; and 9.5 Mb genomic regions for high-grade myopia spanned between SNP markers rs11977885/rs10950639, rs11770622/rs9719399, and rs4763417/rs10842388 on chromosomes 7p22.1-7p21.1, 7p12.3-7p11.2, and 12p12.3-12p12.1, respectively.
近视是最常见的人类眼部疾病，其病因复杂，涉及遗传和环境因素。迄今为止，在不同地理区域的家族中已鉴定出多个近视基因座。然而，尚未确定致病基因。本研究的目的是对患有高度近视的波兰家族进行特征分析，包括遗传分析。
42个患有非综合征性高度近视的波兰多重家庭参与了本研究。所有家庭成员均接受了详细的眼科检查，基于球镜屈光不正，高度近视被定义为≤ -6.0屈光度（D）。使用Affymetrix Human SNP Array 6.0对一个有多个患病个体的选定家族（HM - 32）进行了全基因组单核苷酸多态性（SNP）高密度连锁扫描。
非参数连锁分析在家族HM - 32中分别在染色体7p22.1 - 7p21.1（[NPL] 8.26；p = 0.006）、染色体7p12.3 - 7p11.2（[NPL] 8.23；p = 0.006）和染色体12p12.3 - 12p12.1（[NPL] 8.02；p = 0.006）上鉴定出三个新的基因座。通过从连锁面板中系统地剔除SNP，解决了由于密集SNP图谱导致的连锁不平衡对连锁的影响。
对患病个体中信息性交叉进行单倍型分析，分别在染色体7p22.1 - 7p21.1、7p12.3 - 7p11.2和12p12.3 - 12p12.1上确定了高度近视的基因组区域，跨度分别为12.2；10.9；和9.5 Mb，位于SNP标记rs11977885/rs10950639、rs11770622/rs9719399和rs4763417/rs10842388之间。
