第十章基因組學(xué)ppt課件

1、 第十章 基因組學(xué) (Genomics);nStructural Genomics 構(gòu)造基因組學(xué)構(gòu)造基因組學(xué)nFunctional Genomics 功能基因組學(xué)功能基因組學(xué)n Transcriptomics 轉(zhuǎn)錄物組學(xué)轉(zhuǎn)錄物組學(xué)n Proteomics 蛋白質(zhì)組學(xué)蛋白質(zhì)組學(xué);第一節(jié) 真核生物基因組組成Organization of Eukaryotic Genome 1. C value paradox and evolutionary complexity C值悖理與進(jìn)化的復(fù)雜性值悖理與進(jìn)化的復(fù)雜性 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 高度反復(fù)序列n 5300bp , 105 copies nMiddle-repetitiv

3、e sequences 中度反復(fù)序列n 101000 copies nUnique sequences 單拷貝序列; 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散在反復(fù)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 長(zhǎng)分布元件n L1, 6400bp, 100,000 copies;nCluster

5、ed repetitive sequencesn 串聯(lián)反復(fù)序列 n satellite DNA 衛(wèi)星DNA n 100500bp 1005000 kb n minisatellite DNA 小衛(wèi)星DNA n 1160bp 100bp 20kb n microsatellite DNA 微衛(wèi)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.; 第二節(jié) 構(gòu)造基因組學(xué) Structural Genomics Characterize the structure of the genome;一、人類基因組作圖 Mapping human genomeHuman Genome Project;An overview of the strategy used in HGP;1. Genetic map 遺傳圖 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 利用重組作圖技術(shù)構(gòu)建的能顯示基因以及其它DNA標(biāo)志在染色體上位置的圖譜;Genetic markers遺傳標(biāo)志遺傳標(biāo)志Alleles are the firstly used landmarks;n DNA markers used as landmarksn RFLP 限制性片段長(zhǎng)度多態(tài)性 n STRP 簡(jiǎn)單串聯(lián)反復(fù)多態(tài)性n SNP 單核苷酸多態(tài)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 簡(jiǎn)單序列長(zhǎng)度多態(tài)性) or

10、microsatellite repeating unit: 29 bp VNTR (variable number of tandem repeats 數(shù)目可變的串聯(lián)反復(fù) ) 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就是指基因組內(nèi)特定核苷酸位置上存在不同的核苷酸且其出現(xiàn)的頻率大于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) 序列標(biāo)志位點(diǎn)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、人類基因定位Locate genes to chromosome1. Linkage analysis of human pedigree;3. Fluorescence in situ hybridization (FISH), 熒光原位雜交;第三節(jié) 功能基因組學(xué) Functional Genomics 1. Characterization of the Proteome by Open Reading

15、 FrameORFAnalysis 利用開(kāi)放閱讀框分析蛋白質(zhì)組 ;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