第十八讲- 北大生命科学学院.pptVIP

2000年6月 白宫的庆典 Venter Collins Public effort- strategy: Celera - strategy: Sequencing Strategies Celera’s view of International Consortium International Consortium’s view of Celera Unfair competition: IC delivering the same goods but with state funding. Unfair competition: Celera delivering the same goods but can use IC data, while IC cannot use Celera data. 遗传图谱(Genetic Map)vs 物理图谱 (Physical Map) 遗传图又称为连锁图（Linkage Map），是指基因或DNA标志在染色体上的相对位置（或距离），通常以基因或DNA片段在染色体交换过程中的分离频率（cM）来表示。cM值越大，两者之间遗传距离越远。 物理图谱是指以已知序列的DNA片段（DNA marker)在染色体上的实际位置，位点之间的距离（图距）以碱基对（bp，kb，Mb）作为测量单位的基因组图。 DNA遗传标记 (DNA marker) 第一代DNA遗传标记是RFLP（Restriction Fragment Length Polymorphism）。DNA序列上的微小变化，甚至1个核苷酸的变化，也能引起限制性内切酶切点的丢失或产生，导致酶切片段长度的变化。 第二代DNA遗传标记SSLP（Simple Seqeuce Length Polymorphism)利用了存在于人类基因组中的大量重复序列，包括重复单位长度在15-65个核苷酸左右的小卫星DNA（minisatellite DNA），重复单位长度在2-6个核苷酸之间的微卫星DNA（microsatellite DNA）。 第三代DNA遗传标记SNP （ single nucleotide polymorphism） ，也是最广泛的遗传标记，是分散于基因组中的单个碱基的差异。这种差异包括单个碱基的缺失和插入，但更常见的是单个核苷酸的替换，即单核苷酸的多态性。 到目前为止已经在人类基因组发现了超过1000万个SNP位点，平均每300bp中就有一个SNP！ RFLP marker SSLP markers WT mut SNP marker Single nucleotide polymorphisms (SNPs) are highly abundant, and are estimated to occur at 1 out of every 1,000 bases in the human genome. SNPs in the coding regions of genes that alter the function or structure of the encoded proteins are a necessary and sufficient cause of most of the known recessively or dominantly inherited monogenic disorders. These SNPs are routinely analysed for diagnostic purposes. However, most SNPs are located in non-coding regions of the genome, and have no direct known impact on the phenotype of an individual. These SNPs are useful as markers in population genetics and evolutionary studies. SNP detection or genotyping The panels illustrate detection of the A-allele of an A-to-G transition. The G-allele would be detected analogously in a parallel reaction. In panel a, hybridization with allele-specific oligonucleotides (ASOs) is shown. Two short ASO probes are used