分子诊断学概论 精品文档.pptVIP

分子診斷學概論 第一章 綜說 overview 疾病發生原因的影響層次 DNA、RNA或蛋白質 分子診斷的目的 偵測這些致病因子是那個層次發生變化 本書著重DNA、RNA的變化 蛋白質層次由原文書章節提供 The Application of Proteomics To Disease Diagnostics 遺傳分子的基礎 生物巨分子：DNA、RNA、蛋白質、糖類、脂質 遺傳物質DNA的發現 1928 格里夫茲 (Griffith)肺炎雙球菌轉形試驗 1942 艾佛瑞(Avery)研究格里夫茲轉形的物質為何? 1952 赫希-卻斯 (Hershey-Chase)以放射線標示噬菌體的蛋白質（S35）和DNA（P32），感染大腸桿菌的實驗 1953 雙螺旋結構的發現 2003 人類基因體計畫的完成 Presented here is a genome sequence of an individual human. It was produced from ~32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments .200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic