利用微阵列比较基因组杂交研究习惯性流产患者基因组微失衡  

Study on micro-unbalance in genome in patients with recurrent spontaneous abortions using array-based comparative genomic hybridization

作　　者：李洁亮[1] 何文茵[1] 魏君[1] 陈欣洁[1] 何文智[1] 孙筱放[1] 

机构地区：[1]广州医科大学附属第三医院妇产科研究所暨广东省产科重大疾病重点实验室,510150

出　　处：《实用医学杂志》2014年第8期1203-1207,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:31171229)

摘　　要：目的:寻找不明原因习惯性流产夫妇基因组微失衡变化,包括拷贝数变异(copy number variations,CNVs)及杂合性缺失(loss of heterozygosity,LOH)。方法 :提取1对不明原因习惯性流产夫妇基因组DNA,利用高分辨率的微阵列比较基因组杂交(array-based comparative genomic hybridization,aCGH)进行检测。结果:在本研究中的习惯性流产夫妇基因组上,未发现可能致病的LOH;而在习惯性流产女方基因组上,我们发现其12号染色体13.31区域有一个392kb大小的4拷贝的CNV,涉及的基因有CLEC4A,POU5F1P3,ZNF705A,FAM66C,FAM90A1,FAM86FP,LOC389634,CLEC6A,CLEC4D,其中CLEC4A,CLEC6A,CLEC4D等在人胎盘滋养层细胞中可检测到表达,主要分布在滋养层细胞表面,早孕期的绒毛及足月胎盘中也可检测到,足月胎盘中表达减少,考虑与炎症及免疫反应,细胞黏附,细胞间信号转导,糖蛋白转运有关。另外,其在胎盘滋养层细胞上的受体可能与HCV,HIV胎盘宫内感染有关。结论:研究表明,基因组的CNVs可能是不明原因习惯性流产的一个原因,高分辨率的aCGH芯片检测技术是一个很好的选择。Objective To investigate the micro-unbalance in genome in a couple with recurrent spontaneous abortions. Methods Genomic DNA from the couple of idiopathic recurrent miscarriage was screened for loss of heterozygosity （LOH） and Copy Number Variations （CNVs） using array-based comparative genomic hybridization （aCGH）. Results The aCGH analysis showed that 4 duplications of CNV with size of 392 kb located at chromosome 12p13.31 were found in wife＇s genome. Some genes were involved, such as CLEC4A, POUSFIP3, ZNFTOSA, FAM66C, FAM9OA1, FAM86FP, LOC389634, CLEC6A, CLEC4D and CLEC4A, among them, CLEC4A, CLEC6A and CLEC4D were expressed in human placenta and trophoblast cells, and in human placenta, especially villi of first trimester, which shared a common protein fold and had diverse functions, including cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. In Addition, the receptor of the gene family may mediated HCV and HIV intrauterine transmission. Conclusions Duplication at chromosome 12p13.31 may associated with recurrent spontaneous abortions in this couple, and the high resolution array-based comparative genomic hybridization （aCGH） may be a good choice for the couples of recurrent miscarriage.

关 键 词：习惯性流产 拷贝数变异 杂合性缺失 微阵列比较基因组杂交 

分 类 号：R714.21[医药卫生—妇产科学]