阳虚质者基因组拷贝数变异小样本研究

摘要

Objective To explore the genetic mechanism of Yang-deficiency constitution by detecting genomic copy number variations (CNVs). Methods Thirty cases of Yang-deficiency constitution and 30 cases of balanced constitution were included according to the standards of Classification and Determination of Constitution in Traditional Chinese Medicine. DNA was extracted from white blood cells in peripheral blood. A genome-wide association study was conducted by using Affymetrix SNP 6.0 platform. CNVs of each sample were analyzed using PennyCNV software. The Yang-deficiency constitution-specific copy number variation regions (CNVRs) of each autosome were identified. CNVR-related genes and their annotations were searched at online Human Genome Browser. Results The mean number of CNVs in balanced constitution group was 12.63±3.39, ranging from 8 to 20. After stepwise elimination of two Yang-deficiency constitution subjects, the mean number of CNVs in Yang-deficiency constitution group was 15.04±8.95, ranging from 2 to 38. A total of 26 CNVRs were identified from 28 Yang-deficiency constitution subjects, including 19 duplicated CNVRs, 6 deleted CNVRs, and 1 mixed type CNVR. Most CNVRs were shared by a few Yang-deficiency constitution subjects, and only 7 CNVRs were shared by more than 5 Yang-deficiency constitution subjects. The functions of representative genes in Yang-deficiency constitution-specific CNVRs were related with extracellular and intracellular signal transduction, metabolic regulation, and immune response, etc. Conclusion Yang-deficiency constitution subjects have some specific genomic CNVs, which might result in Yang-deficiency constitution phenotypes by influencing the expression of genes associated with extracellular and intracellular signal transduction, material metabolism (energy metabolism), and immune response, etc.%目的通过检测全基因组拷贝数变异(CNV)探究阳虚质的遗传机制。方法按照《中医体质分类与判定》标准纳入阳虚质与平和质受试者各30例,提取外周血白细胞DNA,采用SNP6.0基因分型芯片进行全基因组关联分析,采用 PennyCNV 软件分析单个样本 CNVs,逐个常染色体鉴定阳虚质特异的拷贝数变异区域(CNVR),通过人类基因组浏览器检索CNVR的相关基因及其注释。结果平和质组平均CNV数为12.63±3.39,最小值为8,最大值为20；去掉2个异常值后,阳虚质组平均CNV数为15.04±8.95,最小值为2,最大值为38。从28个阳虚质样本中共鉴定出26个CNVR,其中有19个增加型CNVR、6个删除型CNVR、1个混合型CNVR。大多数CNVR仅被少数阳虚质受试者共享,仅7个CNVR被不少于5个阳虚质受试者共享。阳虚质特异的CNVR所包含的代表基因功能涉及细胞内外信号转导、代谢调节、免疫反应等。结论阳虚质者基因组存在一些特异的 CNVs,这些 CNVs 可能通过影响细胞内外信号转导、物质代谢(能量代谢)、免疫反应等相关基因的表达而导致阳虚质“表型”。