Dissertation > Medicine, health > Ophthalmology > Intraocular pressure and glaucoma

Mapping and Identification of Disaese-Causing Genes for Glaucoma

Author WangJunFang
Tutor YinYiBing;YangZhengLin
School Chongqing Medical University
Course Clinical Laboratory Science
Keywords Glaucoma Gene Sites
CLC R775
Type Master's thesis
Year 2007
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Objective: primary glaucoma pedigree Chinese Han genetic linkage analysis and gene sequencing, Screening and identification of new disease-causing gene loci and / or new disease genes and identification of known genes mutation to confirm the causative gene and to clarify the cause disease mechanism. Method: 1. Collected clinical data and blood samples of the Han Chinese primary glaucoma pedigree, extraction of the DNA in the blood samples of the patient's clinical information database. 2. Primary glaucoma known genes, primers were designed for sequencing to exclude known genes. Application of genetic linkage method, known sites and known the gene physical location near STR (short tandom repeat markers) marker screening of known genes and known sites. PCR amplified fragment with 382 STR markers (ABI PRISM Linkage Mapping Sets V2.5-MD), genome-wide scan using ABI3100 Genetic Analyzer. Known sites and gene family, has been ruled out. Internationally recognized method of genetic linkage analysis based on allele (haploid) typing results, the application of the two-point method, respectively, calculated the STR markers LOD value (Lod Score values, indicating that the disease gene and the loci chain the tightness of size) to a maximum LOD score value determined positive sites. 5 near the positive sites the genotypic detection result, according to the fluorescence-labeled STR (single nucleotide polymophism) for finer positioning disease gene to determine the the minimum genetic pitch of MGI (Minimum Genetic Interval). Its disease-causing genes and mutations in MGI screened by the candidate gene approach. Results: 1. Collect clinical and genetic data of the Han Chinese primary glaucoma pedigree. Complete primary open-angle glaucoma the known gene sequencing, and found no known gene mutations. Known genetic loci and gene linkage analysis found its θ = 0.0, LOD value lt; 0, there are several markers LOD score gt;, but add new markers in the vicinity of the LOD score lt; 0, ruled the known genes and genetic linkage sites. Upon completion of the whole genome of the two primary glaucoma pedigrees 382 STR (short tandom repeat markers) scan of the marker. The genome-wide scan found that when θ = 0.0, 0955 Department No. 1, No. 2, on chromosome 8, and several other sites LOD score gt; 1, suggesting the possibility of chain. 0956 Department of the 15th, the 19th chromosome 2 locus LOD score gt; 0, prompted a chain of possibilities. 5. Positive sites may further determine, by the synthesis of new STR markers to identify and eliminate the positive sites, the 0955 has been excluded 1,8 chromosome several sites, is now complete 2 suspicious positive loci on chromosome 5 candidate gene sequencing work, further confirmation of the work is still in progress. 0956 lines 15 and 19 chromosome 2 locus has been ruled out, further analysis of the work in progress. Conclusion: We collect clinical data of the two Han Chinese primary glaucoma pedigree rich genetic resources of glaucoma information. 2 found the new open-angle glaucoma genetic linkage loci discovered a new disease genes and is expected to provide a basis for further elucidate pathogenic mechanisms of open angle glaucoma. In addition an angle closure glaucoma pedigrees expected to find a new chain loci and genes, this will be a new breakthrough in the world, in the world yet to find a closed angle glaucoma linked loci. 4. Conclusion of this research, for research in the field has important academic value, have played a big role for future genetic screening, gene diagnosis and gene therapy.

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