7.1 染色体畸变(结构改变).ppt

1、Chromosomal Abnormalities (染色体畸变),Cytogenetics (细胞遗传学) is the field of study involving examination of the genetic material of the cells. The genetic material (DNA) is contained in chromosomes. Each organism has a characteristic number and arrangement of chromosomes.,Introduction,A karyotype （核型） is

2、a photograph of the chromosomes at metaphase, when they are most easily seen. In a karyotype, the chromosomes are arranged by pairs: alterations in chromosome size (structure) or number are seen here.,Normal Human Karyotype,A normal human cell contains 46 chromosomes: 22 pairs of autosomes（常染色体）, an

3、d two sex chromosomes.,Chromosomal Abnormalities,Chromosomal abnormalities can be of two types. (1) Structural(结构) abnormalities are caused by breaks in the chromosome being incorrectly repaired. “Ends” of broken chromosomes are very unstable in a cell. (2) Numerical(数目) abnormalities are caused by

4、gain or loss of chromosomes.,Common Structural Abnormalities,(1) Deletions (缺失)：loss of genetic material (2) Inversions (倒位): no change in the amount of genetic material,Common Structural Abnormalities,(3) Duplications(重复): gain of genetic material (4) Translocation(易位): no change in the amount of g

5、enetic material (if balanced),(一) Deletions,顶端缺失(Terminal Deletions )：指缺失的区段位于染色体某臂的外端。 中间缺失(Interstitial Deletions )：指缺失的区段位于染色体某臂的中间。,(1)无着丝粒断片：最初发生缺失的细胞在分裂时可见落后染色体无着丝粒断片， (2)顶端缺失 有丝分裂出现因断裂融合双着丝粒染色体后期染色体桥。 减数分裂联会时，有未配对的游离区段。 (3)中间缺失 减数分裂染色体联会时形成缺失环。 注意：较小的缺失往往并不表现出明显的细胞学特征；缺失纯合体减数分裂过程也无明显的细胞学特征。,缺

6、失的细胞学鉴定,缺失的细胞学特征,断裂(breakage)融合(fusion)桥(bridge),顶端缺失的形成(断裂) 复制 姊妹染色单体顶端断头连接(融合) 有丝分裂后期桥(桥) 新的断裂,玉米缺失杂合体粗线期缺失环,果蝇唾腺染色体的缺失环,(1)缺失的后果 打破了基因的连锁平衡，破坏了基因间的互作关系，基因所控制的生物功能或性状可能丧失或异常。 (2)缺失的危害程度 取决于缺失区段的大小、缺失区段所含基因的多少、缺失基因的重要程度、染色体倍性水平。 缺失纯合体致死或半致死 缺失杂合体缺失区段较长时，生活力差、配子(尤其是花粉)败育或育性降低；缺失区段较小时，可能会造成假显性现象或其它异常

7、现象(猫叫综合症)。,缺失的遗传学效应,缺失杂合体的假显性现象,Micro Deletions（教材下册p8 ）,Some genetic syndromes are caused by very small deletions in the chromosome in human. These syndromes have been useful in locating genes involved in specific processes. “Cri du Chat” (cry of the cat) is caused by a small deletion at the tip of

8、 chromosome 5 in human.,1 in 50000 newborns,5p Syndrome (Cat Cry syndrome),Characteristics,Round, moon-shaped face “Cry of the cat” Varying degrees of mental retardation Low set ears,Cri du chat syndrome,(二)Duplication的细胞学特征,重复的遗传学效应,重复对基因平衡的影响：扰乱了生物体本身基因固有的平衡体系，影响了个体的生活力。 有害程度：取决于重复区段基因数量的多少及其重要性，与

9、缺失相比，有害性相对较小，但若重复区段过长，往往使个体致死。 对育性的影响：重复杂合体一般败育，重复纯合体会产生“剂量效应(dosage effect)”。,果蝇复眼的小眼组成数目的剂量效应,Duplication may be caused by unequal crossover in meiosis.,（三）Inversion,(1)臂内倒位(Paracentric inversion)：指倒位发生在染色体的某一臂内，又称为一侧倒位。 (2)臂间倒位(Pericentic inversion)：指倒位发生在两臂之间（含着丝粒），又称为两侧倒位。,Inversion Loop,Invers

10、ions do not change the genetic content of a cell, however they have consequences for meiotic products (gametes) Top: diagram of inversion loop Bottom: EM micrograph of inversion loop during meiosis in a mouse cell,Inversion Loop （倒位环）,Chromosomes with inverted regions can form “inversion loops” when

11、 pairing occurs during meiosis.,Paracentric Inversion Crossover,A crossover involving a paracentric inversion (when the centromere is not in the inverted region) produces altered chromosomes. One product has no centromere (acentric), one has two centromeres (dicentric).,Pericentric Inversion Crossov

12、er,A crossover involving a pericentric inversion (when the centromere is in the inverted region) produces altered chromosomes. One product has gained genetic material (a duplication), one has lost genetic material (a deletion).,Dicentric Chromosomes are Unstable,Dicentric chromosomes can be formed f

13、rom crossovers involving inversions, or in mitotic cells by “healing” of broken ends. Dicentrics undergo a cyclic “breakage-fusion-bridge” during repeated cell divisions.,倒位的细胞学鉴定,细胞学特征 同源染色体联会时： 倒位区段过长倒过来，其余游离 倒位区段较短正常部分配对，其余不配对 倒位区段适中形成倒位环 注意:区分倒位环与缺失、重复环的结构差异, 倒位纯合体无明显细胞学特征,倒位的遗传效应,（1）对基因关系的影响：倒位

14、改变了基因间的连锁关系；因不能正常配对而降低了连锁基因间的重组率。 有害程度：取决于倒位区段的长短，倒位区段过长往往致死。,倒位的遗传效应,（2）对育性的影响：倒位杂合体倒位环内发生交换后，产生的交换型配子(50%)含重复缺失染色单体，这类配子不育。所以倒位杂合体部分不育。倒位纯合的同源染色体联会完全正常，但会产生“位置效应”。 倒位杂合体通过自交（自群繁育），可能产生倒位纯合体后代，这些倒位纯合体后代与其原来的物种不能受精，形成生殖隔离，产生新的变种，促进了生物进化.自学）,(四)Translocation,(1)简单易位(Simple translocation)(单向)：指一个染色体上的

15、某一区段转移到了另一非同源染色体上的现象，故又称为转移。 (2)相互易位(reciprocal translocation)：指两个非同源染色体都被折断，两个断片交换重接到两条被折断的非同源染色体上的现象。,When a part of one chromosome is relocated to another chromosome, the result is called a translocation If parts of two chromosomes “trade places” so no genetic material is lost, it is called a rec

16、iprocal (or balanced) translocation,相互易位的细胞学鉴定,(1)相互易位杂合体 同源染色体联会时 粗线期呈十字形配对 终变期呈四体环（十字形配对结构发生交叉端化后所形成的大环结构，用4表示)或四体链（十字形配对结构发生交叉端化后所形成的链状结构用C4表示) 中期I呈8字形或圆环形（十字形配对结构的交替式分离和相邻式分离） 交替式分离:产生不育配子。相邻式分离：产生可育配子 (2)相互易位纯合体：同源染色体联会一切正常。,Balanced Translocations Pair “Oddly” during Meiosis,The translocated p

17、ortion of the chromosome pairs with its normal homologue in meiotic tetrads Altered segregation affects the gametes: this can be a cause of reduced fertility,Depending on the segregation pattern in a single meiotic division, all of the gametes may have normal DNA content (but half have the transloca

18、tion), or all of the gametes may be defective (have duplication and deletion),Balanced Translocations can Yield Altered Genetic Content in Gametes,易位杂合体的联会和分离,果蝇巨染色体易位图,易位的遗传学效应,（1）降低了连锁基因间的重组率易位改变了基因间的连锁关系，抑制了正常连锁群的重组；联会的紧密程度降低。 （2）易位杂合体半不育 出现假连锁现象因易位改变了基因间的连锁关系，使本应独立遗传的基因出现连锁假连锁。,1960年，Nowell 慢性粒细胞白血病(CML),核型：有“标记性染色体”,Ph染色体,血液学特征,Ph染色体,1960年，首先在美国费城的CML患者骨髓和外周血淋巴细胞中，发现一个很小的异常的近端着丝粒染色体，小于G组染色体(21、22、Y),T(9;22) (22pter22q11:9q349qter) 1973年，Rowley 采用显带技术证实,Ph染色体,der(22)(9; 22) (q34; q11.2),理论意义：首次证实了一种染色体畸变与一种特异性肿瘤的关系，为Boveri提出的“肿瘤染色体理论”提供了实验证据, 是肿瘤遗传学研究的里程碑。,Ph染