唐氏综合征患儿外周血全基因组miRNA表达谱及染色体分布研究

Global miRNA expression profiles and chromosome distribution on peripheral blood in Down Syndrome children

目的:分析唐氏综合征(Down syndrome,DS)患儿与健康儿童外周血单个核细胞miRNA表达谱及其染色体分布特征。方法:采用Illumina测序技术分别对6例DS患儿(DS组)和6例健康儿童(对照组)外周血单个核细胞全基因组miRNA表达谱进行差异表达和染色体分布特征分析,并用Stem-loop q RT-PCR对差异表达miRNA的测序结果进行验证。结果:两样本共表达911个miRNA,编码于738个miRNA基因,在两样本中的染色体分布趋于一致,但表达丰度染色体分布却不同,DS组主要分布于7、13和21号染色体,而对照组主要分布于7和13号染色体。此外,911个miRNA中有114个miRNA在两样本中差异表达显著(差异倍数≥2且P≤0.001),其中DS组有103种高表达,包括21号染色体编码的5个miRNA(miR-99a、let-7c、miR-125b、miR-155和miR-802);11种低表达。结论:DS患儿外周血单个核细胞具有其特定的miRNA表达谱和染色体分布特征,两样本表达丰度差异分布染色体编码miRNA的差异表达可能与DS患者免疫缺陷等相关临床症状的形成有关。

Objective：To investigate the global miRNA expression profiles and chromosome distribution characteristics in peripheral blood mononuclear cells（PBMC） of children with Down syndrome （DS） and without DS. Methods：Illumina deep sequencing technology was used to analyze the global miRNA expression profiles and chromosome distribution in 6 pairs of PBMC samples from DS children（DS group） and non-DS children（control group）. Stem-loop qRT-PCR was employed to verify the results of Illumina deep sequencing technology. Results ：There were 911 miRNAs expressed that were encoded by 738 miRNA genes,which had the same chromosome distribution in both groups. However,the expressive abundance of chromosome distribution was different：DS group was mainly scattered in 7,13 and 21 chromosomes,while the control group was majorly scattered in 7 and 13 chromosomes. Furthermore, 114 of 911 miRNAs were significantly differentially expressed in both groups （difference multiple ≥2, P〈0.001）. In the DS group, 11 miRNAs were low expression and 103 miRNAs were high expression,including 5 miRNAs encoded by 21 chromosome（miR-99a,let- 7c, miR-125b, miR-155, miR-802）. Conclusion：PBMCs of DS children have specific miRNA expression profiles and chromosome distribution characteristics. Differences of expressive abundance of miRNAs encoded by the chromosome may be associated with clin-ical symptoms in DS patients, such as immune deficiency.