一个原发性痛风大家系全基因组测序结果及初步分析

A whole genome sequencing result and preliminary analysis of a primary gout pedigree

目的通过对一原发性痛风大家系进行全基因组测序,筛选与疾病有关的新的基因突变并进行初步分析。方法收集一典型痛风家系(4代35人,9例患者)的临床资料,绘制家系图谱。收集血液标本抽提外周血基因组DNA,进行全基因组测序分析。通过软件分析比对,筛选出变异序列及相关突变位点。同时在家系及正常对照中进行检测验证。应用生物信息学软件预测突变对基因表达的影响。结果基于测序结果,进行高级信息学分析,在PLAA基因第8外显子附近靠近5′端筛选出致病杂合突变1040-8 A>G;验证结果显示,该家系中所有痛风患者均有1040-8 A>G位点的杂合突变,而该家系的非痛风者和200名正常对照者中均未发现该突变;生物信息学分析提示该突变可能影响PLAA的基因表达,但不影响PLAA mRNA的结构。结论PLAA基因1040-8 A>G突变在家系中存在与患者共分离,新发现的PLAA基因可能为痛风的一个致病基因。

Objective To screen gene mutation information of gout pedigree through whole genome sequencing and to carry out preliminary analysis.Methods One typical gout pedigree was selected as the study subjects.The clinical data and the peripheral blood samples were collected and constructed charts of the pedigree.DNAs were extracted from peripheral blood and analyzed by the whole genome sequencing,and by the software analysis and comparison,screening out the pathogenic genes and related mutations.Then the verifications were conducted in the family members and the controls.Bioinformatics software was applied to predict the effect of mutation on gene expression.Results Based on the sequencing results,advanced informational analysis was performed to screen out the mutations 1040-8 A>G near the 5′end near the exon 8 of the PLAA gene.The results showed that all the gout patients in the family had 1040-8 A>G sites,and none of the mutants were found in the non-gout group and 200 controls;bioinformatics analysis suggested that the mutation could affect PLAA gene expression,but not affecting PLAA mRNA structure.Conclusion PLAA gene 1040-8 A>G mutation is separated from patients in the gout pedigree,and the newly discovered PLAA gene may act as a gout pathogenic gene.