WTO規(guī)則--新版(8)

1、 第七章第七章 遺傳物質(zhì)的變異遺傳物質(zhì)的變異及修復(fù)機(jī)制及修復(fù)機(jī)制 Molecular mechanism of mutation and DNA repair Chromosome Aberration（染色體畸變） Changes in Chromosome Structure Changes in Chromosome Number Gene Mutation 第一節(jié)第一節(jié) 染色體畸變?nèi)旧w畸變 Chromosome Aberration 一、染色體結(jié)構(gòu)變異 Changes in Chromosome Structure Sometimes chromosome mutation can

2、be detected by microscopic observation Polytene chromosome (多線染色體） 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（幼蟲） of Drosophila and other two-winged flies The polytene str

3、uctures are formed by repeated replication of the DNA (10005000), but without separation of the replicated chromatin strands in a mitotic process Types of changes in chromosome structure Deletion 缺失 Duplication 重復(fù) Inversion 倒位 Translocation 易位Mechanisms of change Chromosome rearrangements can arise

4、through physical breakage(斷裂)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 radiation1. DeletionA deletion is a lost portion of a chromosome Terminal deletion 末端缺失 Interstitial deletion 中間缺失 The e

5、ffects of deletions depend on their size Small deletion within a gene inactivates the gene Large deletion affect more adjacent genes Deletion homozygote(純合體) is often lethal Deletion heterozygote (雜合體) is often harmful Heterozygous for a multigenic deletion may not surviveDeletion heterozygote forms

6、 deletion loop during meiotic division 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 假顯性 )Using deletion to locate genes2. Duplication A duplication is a repeated part of the ge

7、netic material 串聯(lián)重復(fù)(tandem duplication) 非串聯(lián)重復(fù)(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 Proposed generation of variant human hemoglobin subunits by

8、 unequal crossing-over in the - genetic region. 3. Inversion Inversion rearrange the linear gene sequence pericentric inversion 臂間倒位 paracentric inversion 臂內(nèi)倒位 Origin of InversionAn inversion can affect phenotype Inversion reduce the frequency of crossing-over and recombination Inversion homozygote

9、is normal Inversion heterozygote form an inversion loop in meiosis平衡致死系(balanced lethal system) 利用倒位雜合體或緊密連鎖基因的交換抑制效應(yīng)，保存隱性致死基因，又叫永久雜種(permanent hybrid) 展翅展翅 D+/+ +G/+ 粘膠眼粘膠眼 +/+ D+/+ D+/+G +/+G 自交自交 D+/D+ D+/+G +G/+G 致死致死 展翅、粘膠眼展翅、粘膠眼 致死致死 4. Translocation Translocation alter the location of chromos

10、omal segments Reciprocal translocations 相互易位 Nonreciprocal translocation 非相互易位 羅伯遜式易位羅伯遜式易位 Translocation homozygote is normal Translocation heterozygote form a crosslike configuration in meiosis Translocation heterozygote diminishes fertility and results in Pseudolinkage(假連鎖)Some kinds of cancer ar

11、e associated with translocation in somatic cells二、染色體數(shù)目的變異 Changes in Chromosome Number chromosome set(染色體組染色體組 )：The group of different chromosomes that carries the basic set of genetic information of a particular species. euploid(整倍體整倍體 ) ：Organisms with complete chromosome sets aneuploid(非整倍體非整倍體

12、 ) : Organisms gain or lost one or more chromosomes, but not a chromosome set 1. Euploid (整倍體 ) 單倍體(haploid) 或一倍體(monoploid): n 二倍體(diploid): 2n 多倍體(polyploid) : 三倍體(triploid) 3n 四倍體(tetraploid) 4n 六倍體(hexaploid) 6n 八倍體(octploid) 8n Monoploid organisms are usually infertile, but they are important i

13、n plant breeding. Polyploid autopolyploids 同源多倍體 allopolyploids 異源多倍體 Many polyploid plants are larger than their diploid counterparts Triploids are almost always sterile Tetraploid Allopolyploid 異源多倍體 Some allopolyploids have agriculturally desirable traits derived from two species2. Aneuploid(非整倍體

14、 ) 雙體(disomic)：2n ABCD/ABCD 單體(monosomic): 2n-1 ABCD/ABC 缺體(nullisomic): 2n-2 ABC/ABC 三體(trisomic): 2n+1 ABCD/ABCD/A 四體(tetrasomic): 2n+2 ABCD/ABCD/AA 雙三體(double trisomic): 2n+1+1 ABCD/ABCD/AB nNondisjunction （不分離）in mitosis or meiosis is the cause of most aneuploids. Aneuploid and human diseases 第二

15、節(jié)第二節(jié) 基因突變基因突變 Gene mutation一、基因突變的類型基因突變的類型( 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形態(tài), biochemical, behavior, regulatory, lethal, co

16、nditional) 二、突變的特點(diǎn)突變的特點(diǎn) (characteristics of mutation)1. Random, but exists hot spots of mutation 5-methylcytosine 5-甲基胞嘧啶2. Mutations are usually, but not always spontaneous Spontaneous mutation Adaptive mutation Cairns J. et.al 1988 Nature 335:142-145 The origin of mutants3. Mutation occurs at very

17、 low rate, the mutation rate varies among organisms and genes 4. Forward mutations occur more often than reverse mutations5. Multiple directions三、突變的檢測(cè) (detection of mutation)1. Detection in bacteria and fungi（真菌）2. Detection in Drosophila（果蠅） CLB method C: an inversion L: a recessive lethal allele

18、B: the dominant duplicated Bar eye gene 3. Detection in humans pedigree analysis四、突變的分子基礎(chǔ) (Molecular basis of mutation)1. Spontaneous mutation（自發(fā)突變） Errors in DNA replication （復(fù)制錯(cuò)誤）Transitions 轉(zhuǎn)換 Transversions 顛換 Frameshift mutations 移碼突變 Deletions and duplications 缺失和重復(fù) Spontaneous lesions (自發(fā)損傷) D

19、epurination （脫嘌呤） Deamination （脫氨基） Oxidatively damaged bases （氧化性損傷堿基）2. Induced mutations 誘發(fā)突變 Radiation 射線 Ultraviolet（UV） irradiation 紫外線 Ionizing radiation 離子射線 Chemical mutagens 化學(xué)誘變劑 Base analogs 堿基類似物 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 Alkylating agents（烷化劑） ethylmethanesulfonate (EMS) 乙基甲烷磺酸 nitrosoguanidine (NG) 亞硝基胍 Intercalating agents （DNA插入劑） proflavin 原黃素 acridine orange 吖啶橙 Cause ba