中国汉族人群儿童孤独症的UBE3A基因突变筛查

发布时间：2018-12-15 04:38

【摘要】：目的15q11-13区域是人类基因组中最复杂的染色体区域之一,研究发现15q11-13区缺失和重复个体中存在孤独症样的临床表型,而15q11-13区重复也是孤独症人群中最常见的拷贝数变异。UBE3A基因位于15q11-13区,编码泛素-蛋白连接酶E3A,是孤独症重要的候选基因。本研究在中国汉族孤独症人群中筛查UBE3A基因变异并分析变异与孤独症的相关性。方法1.通过高分辨率熔解曲线(high resolution melting,HRM)和Sanger测序法对192例儿童孤独症患者(病例组)和192例健康对照(对照组)进行UBE3A基因编码区及其邻近非编码区域的突变筛查。2.对突变筛查发现的变异通过HRM的方法扩大样本验证,分析变异的分布频率在孤独症患者和健康对照组间的差异。结果1.在UBE3A基因的第4个编码区域(CDS4)发现一个已知的单核苷酸置换(TC,rs150331504),为同义突变。在筛查样本中,病例组有4例、对照组有1例携带该变异;扩大样本后,该变异在病例组和对照组中的发生频率分别为10/384、5/384,两组间差异无统计学意义。分析比较携带rs150331504不同等位基因所编码m RNA的最小自由能,结果显示rs150331504的等位基因T和等位基因C的最小自由能存在一定差异,说明该变异可能改变了转录过程中的m RNA二级结构。其余编码区域未见变异。2.在UBE3A基因第2个编码区域(CDS2)上游288bp处发现了5个碱基的插入缺失(AACTC+/-,rs71127053),在筛查样本中病例组和对照组的频率均是16/192(5%)。扩大样本后进行关联分析,rs71127053的等位基因和基因型分布频率在病例组和对照组间无显著性差异(P0.05);在不同遗传模式下,rs71127053的基因型分布频率在病例组和对照组间无显著性差异(P0.05)。结论在中国汉族人群中,UBE3A基因可能与孤独症不相关。
[Abstract]:Objective the 15q11-13 region is one of the most complex chromosomal regions in the human genome. 15q11-13 repeat is also the most common copy number variation in autistic population. UBE3A gene is located in 15q11-13 region and encodes Ubiquitin protein ligase E3A, which is an important candidate gene for autism. In this study, the mutation of UBE3A gene was screened in Chinese autistic population and the correlation between mutation and autism was analyzed. Method 1. High resolution fusion curve (high resolution melting,HRM) and Sanger sequencing were used to screen for mutations in the coding region of UBE3A gene and its adjacent noncoding region in 192 autistic children (case group) and 192 healthy controls (control group). 2. The mutations found in mutation screening were expanded by HRM to analyze the differences in the frequency of mutation distribution between autistic patients and healthy controls. Result 1. A known single nucleotide substitution (TC,rs150331504) was found in the fourth coding region (CDS4) of the UBE3A gene. In the screening sample, there were 4 cases in the case group and 1 case in the control group, and the frequency of the mutation in the case group and the control group was 10 / 384 / 5 / 384 after expanding the sample, and there was no significant difference between the two groups. The minimum free energy of m RNA encoded by different alleles of rs150331504 was analyzed and compared. The results showed that the minimum free energy of allele T and allele C of rs150331504 were different to some extent. These results suggest that the variation may alter the secondary structure of m RNA during transcription. The other coding regions were not mutated. 2. Five base insertion deletions (AACTC / -, rs71127053) were found in the 288bp upstream of the second coding region (CDS2) of the UBE3A gene. The frequencies of both the case group and the control group were 16 / 192 (5%). There was no significant difference in allele and genotype distribution of rs71127053 between the case group and the control group (P0.05). There was no significant difference in genotype distribution of rs71127053 between case group and control group under different genetic models (P0.05). Conclusion UBE3A gene may not be associated with autism in Chinese Han population.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.94

【相似文献】