文章摘要
孔竹青,倪 磊,朱 淼,卢文祥,白云飞,张志群.一组家族遗传性疾病全基因组测序的分析报告[J].南京医科大学学报,2015,(12):1757~1760
一组家族遗传性疾病全基因组测序的分析报告
Analysis of whole-genome sequencing report of a family with genetic disease
投稿时间:2015-07-29  
DOI:10.7655/NYDXBNS20151220
中文关键词: 家族遗传性疾病  全基因组测序  ANXA3基因  突变
英文关键词: inherited disease  whole-genome sequencing  ANXA3 gene  mutation
基金项目:国家自然科学基金资助(61271054);南京医科大学科技发展基金重点项目 (2013NJMU095)
作者单位
孔竹青 南京市红十字医院神经内科,江苏 南京 210001 
倪 磊 南京医科大学附属南京儿童医院骨科,江苏 南京 210008 
朱 淼 南京迪康金诺生物技术有限公司,江苏 南京 210019 
卢文祥 南京迪康金诺生物技术有限公司,江苏 南京 210019 
白云飞 东南大学生物科学与医学工程学院,江苏 南京 210096 
张志群 南京医科大学附属南京儿童医院骨科,江苏 南京 210008 
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中文摘要:
      目的:临床上发现一组特殊病例,一个家族4代人中均发现有同一种神经肌肉性疾病的患者,症状具体表现为上肢肘关节有不同程度的伸直受限,下肢踝关节似马蹄样畸形,足部高弓畸形?无明显内翻内收现象。本研究拟通过全基因组测序,探讨其发病的致病基因及分子机制。方法:利用高通量测序技术,分别对患儿?具有相似症状的患儿父亲及健康母亲的血液样本进行全基因组测序。利用生物信息学分析筛选疾病相关基因突变,并进一步收集该家族中的其他患病及健康成员的血液样本,利用PCR技术进行验证。结果:生物信息学分析发现一系列突变基因,包括ANXA3基因突变[chr4,c.C820T(p.R274*)]?ATP6V1E2基因突变[chr2,c.G136A(p.V46M)]和HIST1H3A基因突变[chr6,c.C205T(p.Q69*)]等。基于家族更多成员血液样本的PCR实验结果进一步证实,ANXA3为该疾病潜在的致病基因,突变可导致其蛋白质高级结构的改变,可能与该疾病发生有关。结论:本研究为从分子水平上了解该家族遗传性疾病的发生提供了一定的理论参考。
英文摘要:
      Objective:We found a special case in clinic:4 generations in a family were detected neuromuscular disorders. The symptoms included the upper elbows had different degrees of limited straight,lower limbs showed equines deformity,and feet were talipes cavus and were not detected obvious varus and adduction. This research aimed to study genetic mutation and molecular mechanism in crucial gene using whole-genome sequencing. Methods:Blood samples from sick child,father with the similar symptom and healthy mother were used to perform whole-genome sequencing by high-throughput sequencing technique. Bioinformatic analysis was used to filter gene mutations associated with disease. Further PCR validations were performed using blood samples from patients and healthy relatives in the family. Results:A series of gene mutations were obtained based on bioinformatics,including ANXA3 gene mutation(chr4,c.C820T(p.R274*)),HIST1H3A gene mutation (chr 6,c.C205T(p.Q69*)) and MTHFR gene mutation (c.T784C(p.Y262H)). PCR validation using blood samples from the family indicated that ANXA3 may be potential causing gene,and the mutation led to change of three-dimensional structure of ANXA3 protein. Conclusion:These results implicated that the ANXA3 may be related with the occurrence of the disease. This study provides certain reference for further understanding the genetic disease from the molecular levels.
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