染色体基因芯片的临床应用PPT.pptVIP

染色体基因芯片的临床应用 广州市妇产科研究所 广州医科大学附属第三医院 香港中文大学CMA联合实验室 广州省产科重大疾病重点实验室 广东省普通高校生殖与遗传重点实验室 谢英俊 fairyfareyj@ 主要内容 CMA的应用现状 CNV的定义及其与疾病的关系 临床上不同CMA平台的比较 CMA的技术性能，检测流程，数据库的应用，报告的解读 国际上认可的三种遗传检测技术的比较和应用 案例分析 Leading institutions are moving to CMA for Constitutional research Global variation in copy number in the human genome Nature. 2006. CNV We defined a CNV as a DNA segment that is 1 kb or larger and present at variable copy number in comparison with a reference genome. A CNV can be simple in structure, such as tandem duplication, or may involve complex gains or losses of homologous sequences at multiple sites in the genome. Global variation in copy number in the human genome , Nature , 2006 CMA Chromosomal Microarray Analysis chromosomal microarray Molecular karyotyping(分子核型分析) Encompasses all types of array-based genomic copy number analyses, including array-based comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) arrays 分子核型（CMA） 临床检测平台 Array-CGH Array-SNP 比较 LD: Oxford Gene Technology CytoSure ISCA uniparental disomy MD: Agilent custom array HD: Affymetrix CytoScan HD All three CN+SNP arrays were able to detect CNVs 100 kb in size, which is more sensitive than the American College of Medical Genetics and Genomics recommendation of 400 kb. 某些类型的芯片可鉴定出血缘关系或非亲生关系的证据。所以 报告的信息类型和数量取决于使用的芯片类型以及开展分析的实验室的政策 CMA检测平台 CytoScan HD , CytoScan 750K芯片的特点 全基因组覆盖，与临床相关的基因区域特别加密： 750,000 个生物学标记 200,000个 SNPs 探针，能检测3Mb LOH 550,000 个CNV探针，200kb的卓越的分辨率. 遗传学区域加密覆盖 1 marker per 1 kb for ISCA, Cancer Genes X Chromosome 1 marker per 2 kb RefSeq genes Percentage of genes covered (25 markers/100 kb) CytoScan HD CytoScan 750K ISCA constitutional genes (340) 100% 100% Cancer genes (526) 100% 100% OMIM Morbid genes (2,640) 98% 83% X