第十章基因组学ppt课件

1、 第十章 基因组学 (Genomics);nStructural Genomics 构造基因组学构造基因组学nFunctional Genomics 功能基因组学功能基因组学n Transcriptomics 转录物组学转录物组学n Proteomics 蛋白质组学蛋白质组学;第一节 真核生物基因组组成Organization of Eukaryotic Genome 1. C value paradox and evolutionary complexity C值悖理与进化的复杂性值悖理与进化的复杂性 C value: the amount of DNA contained in the h

2、aploid genome of a species ;C value paradoxnThe increase of total DNA content are dramaticnDNA content in closely related organisms can vary 10-fold or moren n There are large scale of non-coding sequence in eukaryotic genome;nHighly repetitive sequences 高度反复序列n 5300bp , 105 copies nMiddle-repetitiv

3、e sequences 中度反复序列n 101000 copies nUnique sequences 单拷贝序列; Gene family基因家族基因家族: a set of genes in one genome all descended from the same ancestral gene.All members in a family may locate on the same (gene cluster 基因簇) or different lociThe genes in a family can be identical or not identical;Psudogene

4、 假基因 An inactive gene derived from an ancestral active gene.;nDispersed repetitive sequences散在反复序列 result from transposition n short interspersed nuclear elements, SINEsn 短分布元件 , 500bp , 500,000 copiesn Alu familyn long interspersed nuclear elements, LINEsn 长分布元件n L1, 6400bp, 100,000 copies;nCluster

5、ed repetitive sequencesn 串联反复序列 n satellite DNA 卫星DNA n 100500bp 1005000 kb n minisatellite DNA 小卫星DNA n 1160bp 100bp 20kb n microsatellite DNA 微卫星DNA n 15 bp , (CA)550, account for 0.5%;nCentromeric and Telomeric DNA sequencen n Centromeren Yeast centromere region; Telomere Two types of telomere se

6、quences Telomeric DNA sequences: consists of short tandem repeats, that contributes to the stability and integrity of the chromosomes Tetrahymena, GGGGTT Human, GGGATTTelomere-associated sequences: is repetitive and is found both adjacent to and within the telomere. The sequences vary among organism

7、s.; 第二节 构造基因组学 Structural Genomics Characterize the structure of the genome;一、人类基因组作图 Mapping human genomeHuman Genome Project;An overview of the strategy used in HGP;1. Genetic map 遗传图 The map in which mutant alleles or DNA markers are assigned relative positions along a chromosome on the basis of

8、the recombination frequencies between them 利用重组作图技术构建的能显示基因以及其它DNA标志在染色体上位置的图谱;Genetic markers遗传标志遗传标志Alleles are the firstly used landmarks;n DNA markers used as landmarksn RFLP 限制性片段长度多态性 n STRP 简单串联反复多态性n SNP 单核苷酸多态性 ; RFLPRestriction fragment length polymorphisms;RFLP results from mutations that

9、 eliminate or create a restriction site ;Establishing linkage between a dominant disease gene and a RFLP marker ;12.5cM; STRP (Simple tandem repeat polymorphism) The genetic difference among DNA molecules results from the different repeat timesSSLP (simple-sequence length polymorphism 简单序列长度多态性) or

10、microsatellite repeating unit: 29 bp VNTR (variable number of tandem repeats 数目可变的串联反复 ) or minisatellite repeating unit: 1060 bp; SNP Single-nucleotide polymorphisms nAn SNP is a single base-pair site within the genome at which more than one of the four possible base pairs is commonly found in natu

11、ral populations. n SNP就是指基因组内特定核苷酸位置上存在不同的核苷酸且其出现的频率大于1% ; In human genome, one SNP appears at Every 10003000 bp in protein-coding DNAEvery 5001000 bp in noncoding DNA;nDetect a specific SNPn ASO: allele-specific oligonuleotides;nDNA chip can detect multiple SNPs simultaneouslyn Oligonucleotides chi

12、ps寡核苷酸芯片n ; 2. Physical map A map showing the relatively positions of physical landmarks in a DNA molecule. Common landmarks include the positions of restriction sites and particular DNA sequences.;nOrdering random clones by sequence-tagged sites (STS) 序列标志位点n STS: a DNA sequence, present once per h

13、aploid genome, can be amplified by PCR;A complete physical map of human Y chromosome;3. Genome sequencing ;Alternative strategies for sequencing an entire genome;Genome Sizes and Numbers of GenesWe dont have many genes, but we do have:Alternative Splicing ( 2-3 alternatives/gene)Post-translational M

14、odifications (many more)More Complex Proteins (more domains each, but not more domain types);二、人类基因定位Locate genes to chromosome1. Linkage analysis of human pedigree;3. Fluorescence in situ hybridization (FISH), 荧光原位杂交;第三节 功能基因组学 Functional Genomics 1. Characterization of the Proteome by Open Reading

15、 FrameORFAnalysis 利用开放阅读框分析蛋白质组 ;ORF to detect genesnAny piece of DNA has 6 possible reading frames, 3 in each directionnComputer programs can be used to predict ORFsnA coding region of a gene has motifs such as a start codon (ATG), an ORF and a stop codon (TGA).;Search ORF in the Genomic sequences;nUsing computer to search data bases looking for full or partial homology to known genes characterized in other organisms.n