To screen the TSPAN12 gene for mutation in patients with FEVR: Familial exudative vitreoretinopathy (FEVR) affects retinal vascular system. We have screened patients with FEVR for FZD4 and LRP5 mutation. Recently, TSPAN12 mutations were reported in autosomal dominant FEVR patients. To test if FEVR patients who were negative for FZD and LRP5 mutation tested in our lab may have TSPAN12 gene mutation, we analyzed 19 FEVR patients by screening entire coding sequence. We did not find any mutation. To screen the EYS gene for mutation in patients with ARRP: Retinitis Pigmentosa (RP) is genetically heterogeneous. RP patients have been found with mutations in more than 40 genes. Recently, as much as 5% of ARRP patients in a study were found to have mutation in a gene called EYS. To test if EYS mutations could be found in patient with ARRP, we developed a sequencing assay to screen the entire coding region of EYS. EYS gene is a very large gene composing of 43 exons. We have successfully developed the assay and have analyzed DNA sequence from three normal individuals and 6 patients. We have not found mutation yet. We will continue the analysis on more ARRP patients. To screen the RDS gene for mutation in patients with isolated RP: Retinitis Pigmentosa (RP) is genetically heterogeneous. RP patients have been found with mutations in more than 40 genes. We are often asked to screen mutation in genes with patients visited NEI clinic and other our collaborators as a research project. As collaboration with ophthalmologists from West Virginia University, we have analyzed two patients with RP for CHM gene we developed last year and RDS (PRPH2) we developed this year. We did not found mutation in this gene in these patients. To analyze the PAX2 gene structure in patients collected in earlier studies: This is a continuation of my clinical ophthalmic research from Minnesota and collaboration. We developed a clinical DNA testing of PAX2 gene for Renal-coloboma Syndrome and have been collecting tested samples for genetic heterogeneity analysis. After I joined NEI, we are extending this study to the PAX2 promoter region and other gene loci. Recently, mutations in SRD5A3 gene have been reported in coloboma patients. We tested the hypothesis that SRD5A3 mutation may be presented in our collection of patients. We are screening our patients for SRD5A3 gene entire coding region. To identify the breakpoints of RS1 gene partial deletions in two retinoschisis patients: We are providing clinical genetic testing to NEI clinics for X-lined Juvenile Retinoschisis. We sometime found patients with partial gene deletion. It was difficult to report back to patient each time without knowing the breakpoint of deletion and unable to carry out carrier analysis in mother and sisters. We had a couple of cases recently. We decided to analyze these cases for their genomic breakpoints. With help of a summer student, we have successfully determined the breakpoints and defined the deleted sequences. To search for gene mutation by exome sequencing in CRD patients: This year, we also investigated into the new technologies for our patient studies. We selected 8 CRD patients who was studied before with no mutation in selected genes. We have performed exome sequencing analysis. We have completed the data collection and data analysis is in progress. To analyze promoter and intronic genomic abnormalities in Tyrosinase gene: This is also a continuation of my clinical research from Minnesota and collaboration with Dr. Bearing from NCI/NIH. I have been collecting tested samples for genetic heterogeneity analysis of TRY in Ocular-Cutaneous Albinism. We have a research fellow joined my lab last year. She has token this project. She is focusing on the promoter region and has identified methylated CpG island through several approaches. She is working to correlate the methylation with regulation of gene expression at mRNA level through several cell lines and developing different approaches to identify enhancer/suppressor regions. To analyze common variations in CFTR gene and NOS3 gene in CF mutation carriers: This is also a continuation of my clinical research from Minnesota and collaboration with clinicians from University of Minnesota Medical Center and Dr. Garry Cutting from Johns Hopkins Medical Institutes. We have surveyed 153 obligate CF mutation carriers from Minnesota and surrounding area for their sinus problem. We are exploring the frequency of chronic rhinosinusitis in CF carriers. We will present a poster at the 2011 ASHG meeting for our results. We were invited to write a book chapter for chronic rhinosinusitis and published in this year. To perform resequencing chip analysis in patients with isolated eye abnormalities collected in earlier studies: This project started several years ago in OGFVB. We developed a screening tool by the resequencing CHIP on 93 genes provided an opportunity for these samples on hold. With Dr. Miller and Dr. Sohrabys help, we were able to continue the project using core facility by Dr. Swaroop and Matthew Brooks. We were eventually established the testing protocol. Our manuscript is in revision for publication. We are continuing to analyze more patients by a graduate student sponsored by Chinese Government Fellowship. To develop new screening tool for retinal disease related genes: Recent development of next-gen sequencing technology has been reaching every corner of human disease studies. To take the advantage of next-gene technology, we are developing a new platform for high throughput sequencing using the RainStorm Microdroplet PCR technology and PGM systems. This project is in progress. The primer library designing is completed. We are validating the primer library.
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