[Frontiers in Bioscience 16, 2052-2059, June 1, 2011]

Confirmation and further mapping of the GLC3C locus in primary congenital glaucoma

Xueli Chen1,2 Yuhong Chen1,2, Li Wang1,2, Deke Jiang3, Wenzhang Wang3, Mingying Xia4, Long Yu3,4, Xinghuai Sun1,2

1Eye and ENT Hospital, Department of Ophthalmology and Vision Science, Fudan University, 83 Fenyang Road, 200031, Shanghai, China, 2Shanghai Medical College of Fudan University, 138 Yixueyuan Road, 200032, Shanghai, China, 3Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, 200433, Shanghai, China, 4Institute of Biomedical Science, Fudan University, 138 Yixueyuan Road, 200032, Shanghai, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Sample diagnosis and collection
3.1.2. Clinical examination
3.1.2. Case diagnosis
3.1.3. Sample collection
3.2. Genotyping
3.2.1. Short tandem repeat (STR) typing
3.2.2. Single nucleotide polymorphism (SNP) typing
3.3. Data analysis
3.3.1. Transmission disequilibrium test (TDT)
3.3.2. Haplotype analysis
4. Results
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

We investigated the relationship between primary congenital glaucoma (PCG) in the Chinese Han population and its candidate locus GLC3C. 152 nuclear families (patients with normal parents) without carrying the CYP1B1 mutation were enrolled. Fluorescence Labeled Multiplex-PCR was used to genotype 12 short tandem repeats (STRs) within GLC3C region and transmission disequilibrium test (TDT) was used to analyze the association between PCG and these STR markers. Sixteen haplotype tag single nucleotide polymorphisms (htSNPs) were chosen from the location where the TDT tests showed positive results. Matrix-assisted laser desorption/ionization Time-of-flight (MALDI-TOF) mass spectrometry was used to perform SNP genotyping Haplotypes constructed from these SNPs were analyzed. The TDT results of STRs in the GLC3C area indicated that D14S279, D14S555 and D14S74 have significant transmission disequilibrium signals (p = 0.0210, 0.0096 and 0.0034), with a genetic distance of 0.006cM among them. Significant transmission disequilibrium (P=0.0010) occurred between the haplotype TAACG of rs2111701- rs4020123- rs4903696- rs11159318- rs177216 and the disease. Detection of disease causing genes within this region needs further study.