先天性核性颗粒状白内障家系致病基因的定位与突变检测

发布时间：2018-11-23 10:15

【摘要】：目的对中国一常染色体显性遗传先天性核性颗粒状白内障家系进行致病基因的定位与候选基因突变检测。方法采集家系成员外周静脉血,提取基因组DNA。选用ABI公司提供的荧光标记物进行基因扫描。首先对已报道的先天性白内障候选区域进行初步扫描,数据经连锁分析,计算对数优势计分(LOD)值。在连锁阳性区域内选取更加精细的荧光标记物进行进一步精细扫描。数据经连锁分析,确定最大LOD值。数据汇总进行单体型分析。候选基因直接测序检测基因突变。结果两点间连锁分析结果,在荧光标记物D13S175处获得最大LOD值Zmax=5.90(θmax=0.00)。排列单体型后将致病基因定位于荧光标记物D13S1316和D13S1275之间,位于染色体13q12.11。候选基因直接测序发现α3连接蛋白基因(GJA3)第2外显子第427碱基一个G-A的点突变,导致多肽编码序列的第143位甘氨酸变为精氨酸(G143R)。结论本研究将一中国先天性核性颗粒状白内障家系的致病基因定位于染色体13q12.11区域内,并在GJA3基因发现一个新的点突变。
[Abstract]:Objective to locate the pathogenic genes and detect the mutation of candidate genes in an autosomal dominant congenital nuclear granular cataract family in China. Methods Peripheral venous blood was collected from family members and genomic DNA. was extracted. The fluorescent markers provided by ABI were used for gene scanning. First, the reported candidate areas of congenital cataract were scanned, and the logarithmic dominance score (LOD) was calculated by linkage analysis. A more refined fluorescent marker was selected in the linkage positive area for further fine scanning. The maximum LOD value was determined by linkage analysis. The data were collected for haplotype analysis. Candidate genes were directly sequenced to detect gene mutations. Results the maximum LOD value Zmax=5.90 (胃 max=0.00) was obtained at the fluorescent marker D13S175. After the haplotypes were arranged, the pathogenic genes were located between the fluorescent marker D13S1316 and D13S1275, and located on chromosome 13q12.11. Direct sequencing of the candidate gene revealed a G-A mutation in exon 2 of 伪 3 connexin gene (GJA3), which led to the transformation of glycine into arginine (G143R) at the 143rd position of peptide coding sequence. Conclusion in this study, the pathogenic gene of a Chinese family with congenital nuclear granular cataract was located in the 13q12.11 region of chromosome, and a new point mutation was found in the GJA3 gene.
【作者单位】：哈尔滨医科大学附属第一医院眼科;哈尔滨医科大学附属第三医院医务科;
【基金】：黑龙江省教育厅面上项目(12531223)
【分类号】：R776.1

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