全基因组拷贝数变异的鉴定和基于家系的艾弗利诺角膜营养不良的关联研究。

Identification of genome-wide copy number variations and a family-based association study of Avellino corneal dystrophy.

机构信息

Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Shinsu-dong, Mapo-gu, Seoul, Republic of Korea.

出版信息

Ophthalmology. 2010 Jul;117(7):1306-12.e4. doi: 10.1016/j.ophtha.2009.11.021. Epub 2010 Mar 3.

DOI:10.1016/j.ophtha.2009.11.021

PMID:20202685

Abstract

OBJECTIVE

To determine the association of identified copy number variations (CNVs) in whole genome with the risk of Avellino corneal dystrophy (ACD) in a Korean population.

DESIGN

Case-control study.

PARTICIPANTS

A total of 146 patients with ACD and 226 control subjects.

METHODS

A total of 193 trios were genotyped by the Illumina HumanHapCNV370-Duo BeadChip (370,404 markers) (Illumina, Inc., San Diego, CA). The intensity signal (log R ratio) and allelic intensity ratio (B allele frequency) of each marker in all individuals were obtained by Illumina BeadStudio software (Illumina, Inc.). To obtain authentic CNVs in this study, we performed a family-based CNV validation and family-based boundary mapping using the PennCNV algorithm, which incorporates multiple factors, including total log R ratio, B allele frequency, and family information, based on an integrated hidden Markov model.

MAIN OUTCOME MEASURES

Statistical comparison and identification of CNVs between case and control using family information.

RESULTS

We identified 27,267 individual trio CNVs with a median size of 16.2 kb, aggregated in 2245 CNV regions. Most of the identified trio CNVs in this study showed well-defined CNV boundaries and overlapped with those in the Database of Genomic Variants (DGV) (83.4% in number and 79.2% in length). With the common CNV regions (264 CNV regions >5%), we performed a family-based association test with the risk of ACD.

CONCLUSIONS

Two CNV regions (chr6:29978470-29987783 and chr14:59896944-59916129) were significantly associated with the risk of ACD (P=0.05-0.003 and P=0.008, respectively). This study describes the first results of a genome-wide association analysis of individual CNVs with the risk of ACD and shows that 2 novel CNV loci may be involved in the risk of ACD.

FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

摘要

目的

确定全基因组中已识别的拷贝数变异（CNVs）与韩国人群中 Avellino 角膜营养不良（ACD）风险的关联。

设计

病例对照研究。

参与者

共 146 例 ACD 患者和 226 例对照。

方法

使用 Illumina HumanHapCNV370-Duo BeadChip（370404 个标记物）（Illumina，Inc.，圣地亚哥，加利福尼亚州）对 193 个三核苷酸进行基因分型。通过 Illumina BeadStudio 软件（Illumina，Inc.）获得所有个体中每个标记物的强度信号（对数比）和等位基因强度比（B 等位基因频率）。为了在本研究中获得真实的 CNV，我们使用 PennCNV 算法进行了基于家族的 CNV 验证和基于家族的边界映射，该算法基于集成的隐马尔可夫模型，综合了包括总对数比、B 等位基因频率和家族信息在内的多个因素。

主要观察指标

使用家族信息对病例和对照之间的 CNV 进行统计比较和鉴定。

结果

我们鉴定了 27267 个个体三核苷酸 CNV，中位数大小为 16.2kb，聚集在 2245 个 CNV 区域中。本研究中大多数鉴定的三核苷酸 CNV 具有明确的 CNV 边界，与基因组变异数据库（DGV）中的 CNV 重叠（数量上为 83.4%，长度上为 79.2%）。对于常见的 CNV 区域（264 个 CNV 区域>5%），我们进行了基于家族的关联测试，以评估其与 ACD 风险的关系。

结论

两个 CNV 区域（chr6：29978470-29987783 和 chr14：59896944-59916129）与 ACD 风险显著相关（P=0.05-0.003 和 P=0.008）。本研究描述了个体 CNV 与 ACD 风险的全基因组关联分析的首次结果，并表明 2 个新的 CNV 位点可能与 ACD 风险相关。