论文部分内容阅读
目的对2例眼皮肤白化病患者及其家系进行了TYR基因分析,确定其分型和基因型,探讨基因突变对人TYR蛋白结构与功能的影响。方法PCR扩增外周血基因组DNA的TYR基因外显子和外显子-内含子交界区,以DNA序列测定技术检测先证者的TYR基因突变,以生物信息学手段对突变造成的致病性做出合理可能的解释。结果家系1的先证者为929 insC和W 400L突变复合杂合子,家系2中的先证者为G295X突变纯合子,其中G295X为国际上从未报道过的OCA1致病突变。用ClustalW、蛋白功能分析和二级结构分析均显示家系1中的两种突变和TYR蛋白功能与结构的改变相关。结论应用生物信息学分析方法对TYR基因突变的致病性做出一些合理可能的解释是可行的。
Objective To analyze the TYR gene of 2 patients with ocular albinism and their pedigree, determine the genotype and genotype of TYR, and investigate the effect of gene mutation on the structure and function of human TYR protein. Methods Genomic DNA of TYR gene exons and exon-intron junction regions were amplified by PCR. DNA sequence analysis was used to detect TYR gene mutations in probands. Bioinformatics methods were used to analyze the mutations Reasonable possible explanation. Results The probands of pedigree 1 were 929 insC and W 400L mutated complex heterozygotes. The probands of pedigree 2 were G295X mutant homozygotes, of which G295X was a causative mutation in OCA1 that had never been reported in the world. Using ClustalW, both protein functional analysis and secondary structure analysis showed that both mutations in family 1 and TYR protein function were associated with structural changes. Conclusion It is feasible to make some reasonable explanations for the pathogenicity of TYR mutations using bioinformatics analysis methods.