Exome sequencing identifies ZNF644 mutations in high myopia

Shi, Yi, Li, Yingrui, Zhang, Dingding, Zhang, Hao, Li, Yuanfeng, Lu, Fang, Liu, Xiaoqi, He, Fei, Gong, Bo, Cai, Li, Li, Ruiqiang, Liao, Shihuang, Ma, Shi, Lin, He, Cheng, Jing, Zheng, Hancheng, Shan, Ying, Chen, Bin, Hu, Jianbin, Jin, Xin, Zhao, Peiquan, Chen, Yiye, Zhang, Yong, Lin, Ying, Li, Xi, Fan, Yingchuan, Yang, Huanming, Wang, Jun and Yang, Zhenglin (2011) Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genetics, 7 6: . doi:10.1371/journal.pgen.1002084


Author Shi, Yi
Li, Yingrui
Zhang, Dingding
Zhang, Hao
Li, Yuanfeng
Lu, Fang
Liu, Xiaoqi
He, Fei
Gong, Bo
Cai, Li
Li, Ruiqiang
Liao, Shihuang
Ma, Shi
Lin, He
Cheng, Jing
Zheng, Hancheng
Shan, Ying
Chen, Bin
Hu, Jianbin
Jin, Xin
Zhao, Peiquan
Chen, Yiye
Zhang, Yong
Lin, Ying
Li, Xi
Fan, Yingchuan
Yang, Huanming
Wang, Jun
Yang, Zhenglin
Title Exome sequencing identifies ZNF644 mutations in high myopia
Formatted title
Exome sequencing identifies ZNF644 mutations in high myopia
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
1553-7404
Publication date 2011-06-09
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002084
Open Access Status DOI
Volume 7
Issue 6
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ~97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form.
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Q-Index Status Provisional Code
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Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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