Liu Yutao, Whigham Benjamin T, Wheeler Joshua, Williams Susan E I, Rautenbach Robyn M, Ziskind Ari, Ramsay Michele, Carmichael Trevor R, Ashley-Koch Allison E, Allingham R Rand, Hauser Michael A
Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Mol Vis. 2012;18:2976-81. Epub 2012 Dec 14.
To investigate whether DNA copy number variants (CNVs) in the lysyl oxidase-like 1 (LOXL1) gene are associated with exfoliation glaucoma (XFG) in black South Africans.
Black South African subjects with XFG and age-matched unaffected controls were recruited from the St. John Eye Hospital in Soweto (Johannesburg, South Africa) and East London Hospital Complex (Eastern Cape, South Africa) using standard clinical examination techniques. A customized array comparative genomic hybridization (aCGH) from Roche NimbleGen was designed to cover a 1.5 million base genomic region centered on the LOXL1 gene on chromosome 15. Twenty selected XFG cases were examined using this custom aCGH to identify common CNVs in the LOXL1 gene. The potential DNA copy number variants identified from aCGH were further validated using TaqMan probe-based CNV real-time PCR in a data set containing 91 XFG cases and 52 controls. The frequencies of CNVs in the LOXL1 region were compared between the XFG cases and the controls using Fisher's exact test.
Several DNA CNV variants were identified in the LOXL1 genomic region using aCGH in the selected XFG cases. However, we were unable to validate these candidate CNVs using real-time PCR-based TaqMan CNV assays. There was no significant difference in the frequency of the DNA copy number variants in the LOXL1 region between the XFG cases and the controls.
This represents the first DNA CNV study of LOXL1 in the black South African population with XFG. Our study did not identify any significant DNA copy number alterations in the genomic region containing the LOXL1 gene. This suggests that other as yet unknown causal variants of LOXL1 or variants in other genes in linkage disequilibrium with the LOXL1 locus contribute to the genetic risk of XFG in black South Africans.
研究赖氨酰氧化酶样1（LOXL1）基因中的DNA拷贝数变异（CNV）是否与南非黑人的剥脱性青光眼（XFG）相关。
采用标准临床检查技术，从索韦托（南非约翰内斯堡）的圣约翰眼科医院和东伦敦医院综合院区（南非东开普省）招募患有XFG的南非黑人受试者以及年龄匹配的未受影响对照。设计了一种来自罗氏NimbleGen的定制阵列比较基因组杂交（aCGH），以覆盖以15号染色体上的LOXL1基因为中心的150万个碱基的基因组区域。使用这种定制的aCGH对20例选定的XFG病例进行检测，以鉴定LOXL1基因中的常见CNV。在一个包含91例XFG病例和52例对照的数据集中，使用基于TaqMan探针的CNV实时PCR对从aCGH中鉴定出的潜在DNA拷贝数变异进行进一步验证。使用Fisher精确检验比较XFG病例和对照中LOXL1区域CNV的频率。
在选定的XFG病例中，使用aCGH在LOXL1基因组区域鉴定出了几种DNA CNV变异。然而，我们无法使用基于实时PCR的TaqMan CNV检测来验证这些候选CNV。XFG病例和对照之间LOXL1区域DNA拷贝数变异的频率没有显著差异。
这是首次在患有XFG的南非黑人人群中对LOXL1进行DNA CNV研究。我们的研究未在包含LOXL1基因的基因组区域中发现任何显著的DNA拷贝数改变。这表明LOXL1的其他尚未知晓的致病变异或与LOXL1基因座处于连锁不平衡状态的其他基因中的变异，对南非黑人XFG的遗传风险有影响。
