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1、第九章第九章 染色體畸變染色體畸變染色體結構和數目的變化染色體結構和數目的變化 染色體結構和數目的變化染色體結構和數目的變化染染 色色 體體 畸畸 變變染色體結構的變化染色體結構的變化染色體數目的變化染色體數目的變化CHROMOSOMAL ABERRATIONSChromosomal aberrations:Arise spontaneously or can be induced by chemicals or radiation.Major contributors to human miscarriage流產流產, stillbirths死產死產, and genetic disorde

2、rs遺傳病遺傳病.1/2 of spontaneous abortions流產流產 result from chromosome mutations.Visible (microscope) mutations occur in 6/1,000 live births.11% of men with fertility problems and 6% of men with mental deficiencies智力缺智力缺陷陷 possess chromosome mutations.Chromosomal structure variations 1. Deletion缺失缺失2. Dup

3、lication重復重復3. Inversion倒位倒位 4. Translocation易位易位 染色體數目的變化染色體數目的變化Chromosome number variation1. Aneuploidy非整倍體非整倍體2. Monoploidy單倍體單倍體3. Polyploidy多倍體多倍體Studying chromosome structure mutations:Polytene chromosomes多線染色體多線染色體Occur in insects, commonly in flies (e.g., Drosophila).Chromatid染色單體染色單體 bundl

4、es that result from repeated cycles of chromosome duplication without cell division.Duplicated homologous chromosomes同源染色體同源染色體 are tightly paired and joined at the centromeres著絲粒著絲粒.Chromatids are easily visible under the microscope, and banding patterns corresponding to 30 kb of DNA can be identif

5、ied.Variations in the Structure of Chromosomes染染 色色 體體 結結 構構 的的 變變 化化一、斷裂愈合和交換學說（一、斷裂愈合和交換學說（breakage- reunion hypothesis） 重建（重建（restitution） 非重建性愈合非重建性愈合 不愈合不愈合 染色體結構變異的遺傳學效應染色體結構變異的遺傳學效應 染色體重排：染色體上遺傳信息的順序染色體重排：染色體上遺傳信息的順序排列和鄰接關系發(fā)生改變，影響基因活排列和鄰接關系發(fā)生改變，影響基因活性和表達；性和表達； 核型的改變：若產生結構純合體就會影核型的改變：若產生結構純合體就

6、會影響核型；響核型； 形成新的連鎖群形成新的連鎖群 ：染色體易位導致；：染色體易位導致； 減少或增加染色體上的遺傳物質：缺失減少或增加染色體上的遺傳物質：缺失和重復。和重復。 deletionsBegins with a chromosome break.Ends at the break point are sticky, not protected by telomeres.Induced by heat, radiation, viruses, chemicals, transposable elements轉座因子轉座因子, and recombination重組重組 errors.N

7、o reversion不可逆轉不可逆轉; DNA is missing.Cytological細胞學細胞學 effects of large deletions are visible in polytene chromosomes .末端缺失中間缺失中間缺失后配對引起的缺失環(huán)結構聯(lián)會 產生缺失的原因：產生缺失的原因：1、染色體損傷后產生斷裂（末端缺失）或、染色體損傷后產生斷裂（末端缺失）或非重建性愈合（中間缺失）會直接產生非重建性愈合（中間缺失）會直接產生缺失或形成環(huán)狀染色體，經斷裂融合橋缺失或形成環(huán)狀染色體，經斷裂融合橋而產生缺失和重復而產生缺失和重復2、染色體紐結、染色體紐結 3、不等交

8、換、不等交換4、轉座因子可以引起染色體的缺失和倒位轉座因子可以引起染色體的缺失和倒位同源染色體間的不等交換產生的缺失和重復同源染色體間的不等交換產生的缺失和重復（三）缺失的遺傳效應（三）缺失的遺傳效應 1、致死或出現(xiàn)異常、致死或出現(xiàn)異常 貓叫綜合征貓叫綜合征（cri-du-chat syndrome,或或cat cry syndrome）是是Lejeune等在等在1963年首先年首先報導了三例，患兒的哭聲似貓叫，故得名。報導了三例，患兒的哭聲似貓叫，故得名。它是由于它是由于5號染色體短臂缺失（號染色體短臂缺失（5P-）所致所致,因而又稱因而又稱5P- 綜合征，發(fā)病率約為綜合征，發(fā)病率約為1/5

9、萬，萬，女性多于男性，并有生長和智能發(fā)育不全。女性多于男性，并有生長和智能發(fā)育不全。2、假顯性（、假顯性（pseudo-dominate）5 5 P P女嬰患者女嬰患者 ( ( 又稱貓叫綜又稱貓叫綜合征合征 ,5 ,5號染色體短臂缺失號染色體短臂缺失) )This is Charlotte when she was six years old. Charlotte has Cri du Chat syndrome.( ( 貓叫綜合征貓叫綜合征 5 5p- )p- ) effects of deletionsDeletion of one allele of of a homozygous純合純

10、合體體 wild type normal.Deletion of heterozygote雜合體雜合體 normal or mutant (possibly lethal致死的致死的). Deletion of centromere著絲粒著絲粒 typically results in chromosome loss(usually lethal; no known living human has a complete autosome常染色體常染色體 deleted).Deletion mapping:Deletion of the dominant allele of a heteroz

11、ygote results in phenotype of recessive allele(pseudodominance-假顯性假顯性). Deletion mapping used to determine physical locations of Drosophila genes DuplicationDuplication = doubling of chromosome segments.Tandem順向順向, reverse tandem反向反向, and tandem terminal末端末端 duplications are three types of chromosom

12、e duplications.Duplications also result in un-paired loops visible cytologically. Drosophila Bar and double-Bar results from duplications caused by unequal crossing-over 基因型小眼數目 表現(xiàn)型16A區(qū)域片段結構 + / + 2 780 + / + 1 740 + / B 3 360 B 2 90 + / BB 4 45 BB 3 30 B / B 4 70 BB / BB 6 25 基因型基因型 16A區(qū)的數目區(qū)的數目 小眼數

13、小眼數 基因型基因型 16A區(qū)的數目區(qū)的數目 小眼數小眼數雌蠅雌蠅雄蠅雄蠅 Unequal crossing-over produces Bar mutants in Drosophila InversionChromosome segment excises切斷切斷 and reintegrates重建重建 in opposite orientation.Two types of inversions:Pericentric臂間倒位臂間倒位 = include the centromereParacentric臂內倒位臂內倒位 = do not include the centromereG

14、enerally do no result in lost DNA.2、倒位類型：、倒位類型：（1）臂內倒位）臂內倒位（2）臂間倒位）臂間倒位Synaptonemal complexes in mouse meiocytes paracentric inversion臂內倒位臂內倒位:(inverrsion does not include the centromere)Results:1 normal chromosome2 deletion chromosomes(inviable)1 inversion chromosome(all genes present; viable) peri

15、centric inversion臂間倒位臂間倒位:(inversion includes the centromere)Results:1 normal chromosome2 deletion/duplication chromosomes(inviable)1 inversion chromosome(all genes present; viable)3、形態(tài)：倒位環(huán)、形態(tài)：倒位環(huán)倒位雜合體一旦發(fā)生交換：倒位雜合體一旦發(fā)生交換：（1）雙著絲點染色體在隨機位置斷裂；）雙著絲點染色體在隨機位置斷裂；（2）無雙著絲點染色體存在。）無雙著絲點染色體存在。4、遺傳學效應、遺傳學效應（1）產生不正

16、常的性細胞；）產生不正常的性細胞；（2）抑制倒位環(huán)內的基因重組。（平衡致）抑制倒位環(huán)內的基因重組。（平衡致死系死系P289） translocationChange in location of chromosome segment, May change expression = position effect.Intrachromosomal染色體內染色體內Interchromosomal染色體間染色體間Reciprocal相互相互 - segments are exchanged.Non-reciprocal非相互非相互 - no two-way exchange. 類型：類型：1、染色

17、體內易位；、染色體內易位； 染色體間易位。染色體間易位。2、非相互易位；、非相互易位； 相互易位：兩條非同源染色體互相交換相互易位：兩條非同源染色體互相交換染色體片斷。染色體片斷。3、羅伯遜易位（、羅伯遜易位（Robertsonian translocation） 也稱為著絲粒融合或整臂融合（也稱為著絲粒融合或整臂融合（whole-arm fusion）。）。這是一種交互非平衡易位。由兩個這是一種交互非平衡易位。由兩個非同源的端著絲粒染色體的長臂相互重接成一非同源的端著絲粒染色體的長臂相互重接成一條長的中央著絲粒染色體，短臂相互連接成了條長的中央著絲粒染色體，短臂相互連接成了交互的產物，其上含

18、有一些不重要的基因，這交互的產物，其上含有一些不重要的基因，這種小染色體常在細胞分裂中被丟失。種小染色體常在細胞分裂中被丟失。How translocation affects the products of meiotic segregation:Gamete formation differs for homozygotes and heterozygotes:Homozygotes純合子純合子: translocations lead to altered gene linkage基因連鎖基因連鎖.If duplications/deletions are unbalanced, off

19、spring may be inviable不能生存不能生存.Homozygous reciprocal translocations “normal” gametes.Heterozygotes雜合子雜合子: must pair normal chromosomes (N) with translocated chromosomes (T); heterozygotes are “semi-sterile”.Segregation occurs in three different ways (if the effects of crossing-over are ignored):1.Al

20、ternate segregation交互分離交互分離, 50%: 4 complete chromosomes, each cell possesses each chromosome with all the genes (viable).2.Adjacent 1 segregation鄰近分離鄰近分離, 50%: each cell possesses one chromosome with a duplication and deletion (usually inviable).3.Adjacent 2 segregation, rare: each cell possesses o

21、ne chromosome with a duplication and deletion (usually inviable).- chromosome pairing in a translocation heterozygote- dysjunction results in sterility in 50% of the meiotic products-”semi-sterility”ViableOften inviableVery rare-in the rare case where two aneuploid gametes happen to unite,they might

22、 produce a balanced chromosome set Meiosis in translocation heterozygotes with no cross-over.Patau綜合征（13三體） :新生兒中的發(fā)病率約為1：25 000 易位的遺傳學效應：易位的遺傳學效應： 1、位置效應：常染色質的基因重排移到、位置效應：常染色質的基因重排移到異染色質附近，不能表達，如：花斑位異染色質附近，不能表達，如：花斑位置效應（玉米胚乳置效應（玉米胚乳Ccc，果蠅復眼紅）果蠅復眼紅） 2、假連鎖現(xiàn)象：非同源染色體上的基因、假連鎖現(xiàn)象：非同源染色體上的基因間的自由組合受到嚴重抑制。（間的

23、自由組合受到嚴重抑制。（P292）14142121唐氏綜合征唐氏綜合征21-21-三體患者三體患者 ( (殘疾人奧林匹克運動會運動員殘疾人奧林匹克運動會運動員) )第二節(jié)第二節(jié) 染色體數目的變化染色體數目的變化Variation in chromosome numberVariations in Chromosome Number 染色體數目的變化染色體數目的變化非整倍非整倍變化變化整倍整倍變化變化Aneuploidy非整倍體非整倍體Monosomy單體單體= the loss of one chromosome: 2n-1Trisomy三體三體 = the addition of one c

24、hromosome: 2n+1Nullisomy缺體缺體= the loss of one chromosome pair: 2n-2Disomy二體二體 = the addition of one chromosome in a haploid: n+1減數笫一次分裂不分離減數笫一次分裂不分離減數笫二次分裂不分離減數笫二次分裂不分離三體三體三體三體單體單體單體單體正常正常正常正常三體三體單體單體Variation in chromosome number:More about aneuploidy:Not generally well-tolerated in animals; primar

25、ily detected after spontaneous abortion.Four main types of aneuploidy:Nullisomy缺體缺體 = loss of one homologous chromosome pair.Monosomy單體單體 = loss of a single chromosome.Trisomy三體三體 = one extra chromosome.Tetrasomy四體四體 = one extra chromosome pair. Sex chromosome aneuploidy occurs more often than autos

26、ome aneuploidy (inactivation of X compensates).e.g., autosomal trisomy accounts for 1/2 of fetal deaths. Examples of aneuploidyVariation in chromosome numberChanges in complete sets of chromosomes: Monoploidy單倍體單倍體 = one of each chromosome (no homologous pair)Polyploidy多倍體多倍體 = more than one pair of

27、 each chromosome. Variation in chromosome number:Changes in complete sets of chromosomes: Monoploidy = one of each chromosome (no homologous pair)Polyploidy = more than one pair of each chromosome. Monoploidy and polyploidy: Result from either (1) meiotic division without cell division or (2) non-di

28、sjunction不分離不分離 for all chromosomes.Lethal致死致死 in most animals.Monoploidy is rare in adult diploid species because recessive lethal隱隱性致死性致死 mutations are expressed.Polyploidy tolerated in plants because of self-fertilization自體受精自體受精; plays an important role in plant speciation and diversification.Od

29、d- 奇數奇數and even-偶數偶數numbered polyploids; Even-numbered polyploids are more likely to be fertile可育的可育的 because of potential for equal segregation during meiosis.Odd-numbered polyploids have unpaired chromosomes and usually are sterile不育的不育的. Most seedless fruits are triploid.Triploid Set of Chromosom

30、es *Polyploid series Triploid .3x sterile Tetraploid.4x Pentaploid.5x sterile Hexaploid.6x Septaploid.7x sterile Octaploid.8x同源多倍體同源多倍體異源異源多倍體多倍體How do polyploid species arise ? Autopolyploids同源多倍體同源多倍體 (Potato) Chromosome doubling Genomes from the same species Chromosomes form polyvalents多價體多價體 in

31、meiosis Allopolyploids異源多倍體異源多倍體 (Oil seed rape油油菜籽菜籽, wheat小麥小麥) Species hybridisation雜交雜交 Genomes from different species Chromosomes form bivalents二價體二價體 in meiosisRaphanus sativa (2n=18) X Brassica oleracea (2n=18) RR BBRB 18lRaphanobrassica (2n=36) 18ll (allopolyploid)秋水仙素誘發(fā)細胞多倍體秋水仙素誘發(fā)細胞多倍體Barle

32、y大麥大麥 Haploid單倍體單倍體 chromosomedoubling with colchicineSuccess of artificial polyploids Most newly induced polyploids have reduced seed set because of disturbed meiosis Vegetative propagated營養(yǎng)體繁殖營養(yǎng)體繁殖 types very successful (Potato, begonias秋海棠秋海棠 and other flowers) Seed propagated種子繁殖種子繁殖 may develop

33、 most bivalent二價二價 formation to have good seed set (triticale黑小麥黑小麥)Important polyploids Bananas香蕉香蕉 (autotriploid) Alfalfa紫花苜蓿紫花苜蓿 (autotetraploid) Peanut花生花生 (allotetraploid) Bread wheat普通小麥普通小麥 (allohexaploid) Triticale黑小麥黑小麥 (allooctaploid) Sugar beet hybrids甜菜甜菜 (autotriploid) Elatior begonia麗格

34、海棠麗格海棠 (allotriploid)TriticumT.monococcum ( 2n=14 )T.dicoccum ( 2n=28 )T.dicoccoiides ( 2n=28 )T.aestivum ( 2n=42 )( x = 7 )染色體組分析：拿所要分析的多倍體種和比它倍數性低染色體組分析：拿所要分析的多倍體種和比它倍數性低的種雜交，然后觀察雜種減數分裂的配對情況。的種雜交，然后觀察雜種減數分裂的配對情況。T.monococcum T.dicoccoides 21 7ll + 7l AABT.monococcum T.aestivum 28 7ll + 14l AABDT.d

35、icoccoides T.aestivum 35 14ll + 7l AABBDT.dicoccoides T.tauschii 21 21l ABDT.monococcum T.tauschii 14 14l ADT.tauschii T.aestivum 28 7ll + 14l ABDDT.dicoccoides T.searsii 21 7ll + 7l ABBT.monococcum T.searsii ( or T. Aegilops speltoides )AB ( 14l )T. Dicoccoides T.tauschiiABD ( 21l )T. aestivum2n=42 AABBDD ( 21ll )2n=14 DD2n=28 AABB2n=14 BB2n=14 AAT.aestivum Secale cereale2n=14 RR2n=42 AABBDDABDR ( 28l )T.triticale 2n=56 AABBDDRR