基因芯片技术的临床应用.pptx

基因芯片技术(microarray) 的临床应用人类基因及基因组? 23 对染色体--- 2 x 30 亿个碱基? 编码 21,000 个基因 ---编码序列占整个基因组 的1.5%基因及基因组病 （遗传病）. 染色体数量异常? Trisomy 21 （唐氏综合症）? Trisomy 18? Trisomy 13? Sex chromosomal aneuploidies? Mosaic trisomies of other chromosomes. 染色体结构变化More than 200 known disordersMore than 1000 rare abnormalities??单基因病 (more than 8,000).DominantRecessive??肿瘤也是基因及基因组病..线粒体病多基因病? 人类有60多种恶性肿瘤? 所有肿瘤都含有基因及基因组异常Genes + Environments?Thompson Thompson Genetics In Medicine. Eighth Edition中国年出生1600万，出生缺陷发生率在5.6%, 每年新增出生缺陷数约90万例。(婴儿在出生的一年内，体格上出现明显的结构异常和需要手术矫正的畸形）?智力低下?迟发性疾病?-------遗传病的实验室诊断基因芯片（Microarray）一代测序（Sanger Sequencing）原位荧光杂交（FISH）气相色谱-质谱超高效液相色谱酶学检测基因/基因组检测蛋白质及代谢产物检测非测序分子生物学技术（non-DNA techniques）核型分析（Karyotyping）二代测序（NGS）高效液相色谱-串联质谱电感耦合等离子体质谱Chromosome Microarray Analysis (CMA)? Principles of CMA? Current Status of CMA Application for Clinical Service? Future Trends of CMA for Clinical ServicePrinciples of CMAsaCGH techniquesSNP microarray199220032005? Indicating the presence of uniparental disomy (UPD)? Indicating the presence of consanguinity? Indicating the presence of shared ancestry? Identify recessive gene mutations? Confirm CNV calls by checking SNP allele patterns? Increase sensitivity for detection of mosaicism? Identify triploidy for which aCGH fails to detect? Determine parental origin of a de novo CNV? Improves our understanding of genetic aberrations? Enhances the quality control in the diagnostic laboratory workflow? Identify genomic regions with LOH related to tumorigenesisClassification of Copy Number Variants identified by CMAbased on their clinical significances? Pathogenic? Likely pathogenic? Uncertain clinical significance? Likely benign? benignCMA applications for clinical service遗传病的基因及基因组检测肿瘤的基因及基因组检测? 遗传性肿瘤携带者检出? 无症状早期筛查? 分子诊断? 受孕胚胎植入前的基因及基因组检测? 产前筛查及诊断? 新生儿筛查及诊断? 靶向药物的选择? 预后判断? 遗传病病人（儿童及成人）诊断? 健康人群隐性遗传病携带者检出? 治疗监控? 健康及亚健康人群疾病易感基因检测? 复发基因克隆检出Validations of CMA platforms for Clinical Services? Technical Validations? Clinical ValidationsValidation-Agilent aCGH-2