染色体微阵列分析在产前诊断中的应用

染色体微缺失、微重复等基因组结构的畸变是导致胎儿发育迟缓、畸形、流产、死胎和儿童先天性缺陷的内在因素,也是导致围产儿出生缺陷的主要原因。应用染色体微阵列分析(chromosomal microarray analysis,CMA)进行产前、产后遗传病诊断是提高染色体疾病检出率、查明病因并指导家庭下一胎生育的一个有效措施。CMA以外周血、羊水、绒毛或流产物等组织中提取的DNA作为样本,检查全基因组染色体的变化,可以有效检测到常规染色体核型分析难以查出的染色体微缺失、微重复、单亲二倍体和杂合性缺失等基因组失衡现象,是目前国际上最先进的细胞分子遗传学诊断手段。2010年美国细胞遗传学会推荐将染色体芯片代替核型分析作为不明原因智力低下、多发畸形和孤独症疾病的首选诊断手段。

Variation of genome structure such as chromosome microdeletions and microduplication is the cause of intrauterine growth retardation, malformations, miscarriage, stillbirth and congenital defects,which is also the principal cause of perinatal birth defect. Application of chromosomal microarray analysis( CMA) including comparative genomic hybridization( a CGH) and single nucleotide polymorphism-based arrays( SNP-Array) in prenatal and postnatal genetic diagnosis could guide the next births of families by improving the detection rate of chromosomal diseases and identify the pathogeny. The DNA extracts from peripheral blood, amniotic fluid, villus or apoblema etc. were needed for CMA to examine the variations of whole-genome chromosome. With the help of CMA,we can effectively detect genomic variations such as chromosome microdeletion,micro-duplication,uniparental disomy( UPD) and loss of heterozygosity( LOH) that could hardly be found through conventional chromosome karyotype analysis. It has been proved that CMA is the most advanced cellular and molecular genetic diagnosis technique. In 2010,American Society of Cytogenetics recommended CMA,instead of karyotype analysis,as the preferred diagnostics tool to examine the unexplained mental retardation,multiple malformations and autistic disorders.