打印稿突变

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,第七章 遗传物质的变异及修复机制,Molecular mechanism of mutation and DNA repair,Chromosome Aberration,（染色体畸变）,Changes in Chromosome Structure,Changes in Chromosome Number,Gene Mutation,1,第一节 染色体畸变,Chromosome Aberration,一、染色体结构变异,Changes in Chromosome Structure,Sometimes chromosome mutation can be detected by microscopic observation,2,Polytene chromosome (,多线染色体）,A giant chromosome consisting of many identical chromatids lying in parallel register,Found in the nuclei of the salivary gland,（唾腺）,and certain other tissues of the larvae,（幼虫）,of,Drosophila,and other two-winged flies,The polytene structures are formed by repeated replication of the DNA (10005000), but without separation of the replicated chromatin strands in a mitotic process,3,Types of changes in chromosome structure,Deletion,缺失,Duplication,重复,Inversion,倒位,Translocation,易位,4,Mechanisms of change,Chromosome rearrangements can arise through physical breakage(,断裂,),and rejoining(,重接,),of the DNA molecule,Such processes can either occur spontaneously or be induced by treatment with high-energy radiation such as X or,radiation,5,1. Deletion,A deletion is a lost portion of a chromosome,Terminal deletion,末端缺失,Interstitial deletion,中间缺失,6,7,The effects of deletions depend on their size,Small deletion within a gene inactivates the gene,Large deletion affect more adjacent genes,Deletion homozygote(,纯合体,) is often lethal,Deletion heterozygote (,杂合体,) is often harmful,Heterozygous for a multigenic deletion may not survive,Deletion heterozygote forms deletion loop during meiotic division,8,Genetic properties of deletions,The failure of the chromosome to survive as a homozygote,Can not revert to a normal condition,Uncover recessive alleles (pseudodominance,假显性,),Using deletion to locate genes,9,2. Duplication,A duplication is a repeated part of the genetic material,串联重复,(tandem duplication),非串联重复,(nontandem duplication),Most duplications have no obvious phenotypic consequences,Some duplications have phenotypic consequences,The extra region of a duplication is free to undergo gene mutation,10,Proposed generation of variant human hemoglobin subunits by,unequal crossing-over,in the,-,-,genetic region.,11,3. Inversion,Inversion rearrange the linear gene sequence,pericentric inversion,臂间倒位,paracentric inversion,臂内倒位,12,Origin of Inversion,13,An inversion can affect phenotype,14,Inversion reduce the frequency of crossing-over and recombination,Inversion homozygote is normal,Inversion heterozygote form an inversion loop in meiosis,平衡致死系,(balanced lethal system),利用倒位杂合体或紧密连锁基因的交换抑制效应，保存隐性致死基因，又叫永久杂种,(permanent hybrid),15,展翅,D+/+ +G/+,粘胶眼,+/+ D+/+ D+/+G +/+G,自交,D+/D+ D+/+G +G/+G,致死 展翅、粘胶眼 致死,16,4. Translocation,Translocation alter the location of chromosomal segments,Reciprocal translocations,相互易位,Nonreciprocal translocation,非相互易位,17,罗伯逊式易位,18,Translocation homozygote is normal,Translocation heterozygote form a crosslike configuration in meiosis,Translocation heterozygote diminishes fertility and results in Pseudolinkage(,假连锁,),Some kinds of cancer are associated with translocation in somatic cells,19,二、染色体数目的变异,Changes in Chromosome Number,chromosome set(,染色体组,),：,The group of different chromosomes that carries the basic set of genetic information of a particular species.,euploid(,整倍体,),：,Organisms with complete chromosome sets,aneuploid(,非整倍体,),:,Organisms,gain or lost one or more chromosomes, but not a,chromosome set,20,1. Euploid (,整倍体,),单倍体,(haploid),或一倍体,(monoploid): n,二倍体,(diploid): 2n,多倍体,(polyploid),:,三倍体,(triploid) 3n,四倍体,(tetraploid) 4n,六倍体,(hexaploid) 6n,八倍体,(octploid) 8n,21,Monoploid organisms are usually infertile, but they are important in plant breeding.,Polyploid,autopolyploids,同源多倍体,allopolyploids,异源多倍体,22,Many polyploid plants are larger than their diploid counterparts,Triploids are almost always sterile,Tetraploid,23,24,Allopolyploid,异源多倍体,Some allopolyploids,have agriculturally desirable traits derived from two species,25,2. Aneuploid(,非整倍体,),双体,(disomic),：,2n ABCD/ABCD,单体,(monosomic): 2n-1 ABCD/ABC,缺体,(nullisomic): 2n-2 ABC/ABC,三体,(trisomic): 2n+1 ABCD/ABCD/A,四体,(tetrasomic): 2n+2 ABCD/ABCD/AA,双三体,(double trisomic): 2n+1+1 ABCD/ABCD/AB,26,Nondisjunction,（不分离）,in mitosis or meiosis is the cause of most aneuploids.,27,Aneuploid and human diseases,28,第二节 基因突变,Gene mutation,一、,基因突变的类型,(,Types of mutation),Mutation may be classified in various ways,Germinal and Somatic mutation,Spontaneous and induced mutation,Forward mutation and reverse mutation,Other categories of mutation,(morphological,形态, biochemical, behavior, regulatory, lethal, conditional),29,二、,突变的特点,(characteristics of mutation),1. Random, but exists hot spots of mutation,5-methylcytosine,5-,甲基胞嘧啶,30,2. Mutations are usually, but not always spontaneous,Spontaneous mutation,Adaptive mutation,Cairns J. et.al 1988,Nature,335:142-145,The origin of mutants,31,32,33,3. Mutation occurs at very low rate, the mutation rate varies among organisms and genes,4. Forward mutations occur more often than reverse mutations,5. Multiple directions,34,三、突变的检测,(detection of mutation),1. Detection in bacteria and fungi,（真菌）,35,2. Detection in,Drosophila,（果蝇）,CLB,method,C: an inversion,L: a recessive lethal allele,B: the dominant duplicated,Bar,eye gene,3. Detection in humans,pedigree analysis,36,四、突变的分子基础,(Molecular basis of mutation),1.,Spontaneous mutation,（自发突变）,Errors in DNA replication,（复制错误）,Transitions,转换,Transversions,颠换,Frameshift mutations,移码突变,Deletions and duplications,缺失和重复,37,38,Spontaneous lesions,(,自发损伤,),Depurination,（脱嘌呤）,Deamination,（脱氨基）,Oxidatively damaged bases,（氧化性损伤碱基）,39,2. Induced mutations,诱发突变, Radiation,射线,Ultraviolet,（,UV,）,ir,radiation,紫外线,Ionizing radiation,离子射线,40,41, Chemical mutagens,化学诱变剂,Base analogs,碱基类似物,5-bromouracil (5-BU) 5-,溴尿嘧啶,5-BU pairs with G,2-amino-purine (2-AP) 2-,氨基嘌呤,2-AP pairs with C,42,Alkylating agents,（烷化剂）,ethylmethanesulfonate (EMS),乙基甲烷磺酸,nitrosoguanidine (NG),亚硝基胍,43,Intercalating agents,（,DNA,插入剂）,proflavin,原黄素,acridine orange,吖啶橙,Cause base pairs insertions or deletions, Stabilize the loop formed during frameshift,44, The Ames test for mutagens/carcinogens detection,45,五、,动态突变与人类疾病,Dynamic mutation and human disease,fragile X syndrome,(,脆性,X,染色体综合症,),FMR-1,(fragile-X-associated-mental-retardation),46,The possible mechanism of trinucleotide repeat amplification,（三核苷酸重复扩增）,47,定点诱变,六、定点诱变 （,site-directed mutations,）,Reverse Genetics,48,49,第三节,DNA,的修复机制,Mechanisms of DNA repair,1. Photoreactivation repair (,光复活,) in prokaryotes,2. Excision Repair,（切除修复）,in Prokaryotes and Eukaryotes,Excision Repair in,E.coli,50,3. Mismatch Repair,（错配修复）,4. Recombinational repair,（重组修复）,51,5. The SOS repair system -error prone,(,倾向差错,),52,