人类染色体畸变ENGV.ppt

1、10 人类染色体畸变 chromosome aberration,Any type of change in the chromosome structure or number (deficiencies, duplications, translocations, inversions, etc.,Although it can be a mechanism for enhancing genetic diversity, such alterations are usually fatal or ill-adaptive, especially in animals,1. factors

2、 inducing chromosome aberration,A. Ionizing radiation Ionizing radiation produces rearrangements of the genome,When irradiation occurs during the G0/G1 phase of the cell cycle, large-scale rearrangements appear as exchange-type chromosome aberrations at the next mitosis. Such aberrations can alter c

3、ellular phenotypes, and are important in various areas of biology,Medical and public-health applications include perinatal diagnostics characterization of specific cancer types, carcinogenesis risk estimation, radiation biodosimetry and radiotherapeutic treatment planning,Analyzing chromosome aberra

4、tions helps characterize repair/misrepair pathways involved in the processing of DNA damage. Ionizing radiation has some unique features as a probe of such pathways. Compared to other genotoxic agents, it produces copious quantities of DNA double strand breaks (DSBs), and its timing can be controlle

5、d more accurately,Moreover, initial radiation damage has a discrete, stochastic character that can be modulated by using different kinds of radiation (e.g. a -particles versus x-rays) having different ionization densities,The spectrum of different radiation-induced chromosome aberrations is informat

6、ive about the geometry of chromosomes during interphase, and vice versa,Chromosomal instability, in which new aberrations (though often not of the type characteristic of G0/G1 damage) continue to arise many generations after irradiation, represents a form of genomic instability, and genomic instabil

7、ity is prominent during neoplastic progression,B. chemical mutagen A kind of substances, such as drugs or toxins ,that causes chromosomal aberrations of living organisms, or increase the rate of mutation,2. chromosomal aberrations,A. chromosome numerical aberration Numerical aberration is a change i

8、n the number of chromosomes from the normal number characteristic of the human beings,1) Euploidy is the condition of having a normal number of structurally normal chromosomes. Euploid human females have 46 chromosomes (44 autosomes and two X chromosomes,Polyploidy is a multiple of the haploid chrom

9、osome number (n) other than the diploid number (i.e., 3n, 4n and so on,2) Aneuploidy is the condition of having less than or more than the normal diploid number of chromosomes, and is the most frequently observed type of cytogenetic abnormality. In other words, it is any deviation from euploidy, alt

10、hough many authors restrict use of this term to conditions in which only a small number of chromosomes are missing or added,Generally, aneuploidy is recognized as a small deviation from euploidy for the simple reason that major deviations are rarely compatible with survival, and such individuals usu

11、ally die prenatally,The two most commonly observed forms of aneuploidy are monosomy and trisomy,Monosomy is lack of one of a pair of chromosomes. An individual having only one chromosome 6 is said to have monosomy 6. A common monosomy seen in many species is X chromosome monosomy, also known as Turn

12、ers syndrome. Monosomy is most commonly lethal during prenatal development,Trisomy is having three chromosomes of a particular type. A common autosomal trisomy in humans in Down syndrome, or trisomy 21, in which a person has three instead of the normal two chromosome 21s. Trisomy is a specific insta

13、nce of polysomy, a more general term that indicates having more than two of any given chromosome,Another type of aneuploidy is triploidy. A triploid individual has three of every chromosome, that is, three haploid sets of chromosomes. A triploid human would have 69 chromosomes (3 haploid sets of 23,

14、Production of triploids seems to be relatively common and can occur by, for example, fertilization by two sperm,However, birth of a live triploid is extraordinarily rare and such individuals are quite abnormal. The rare triploid that survives for more than a few hours after birth is almost certainly

15、 a mosaic, having a large proportion of diploid cells,3) Chromosome non-disjunction The failure of a pair of homologous chromosomes to separate properly during meiosis. The failure of homologues (at meiosis) or sister chromatids (at mitosis) to separate properly to opposite poles, that is two chromo

16、somes or chromatids go to one pole and none to the other,Non-disjunction can occur during meiosis I or meiosis II. An error in the proper segregation of the chromosomes during both meiosis I and II are pictured below,In meiosis I, the error occurs when the homologous pairs both travel into the same

17、daughter cell. The result is two daughter cells that have two copies of the chromosome (called disomic cells) and two cells that are missing that chromosome (called nullisomic cells,Non-disjunction in Meiosis I,In meiosis II, the error occurs when the sister chromatids will not separate and thus tra

18、vel into the same daughter cell,Non-disjunction in Meiosis II,Fertilization following Meiosis I error,Fertilization following Meiosis II error,B. Chromosome Structural Aberration Structural aberration is a change in chromosome structure detectable by microscopic examination of the metaphase stage of

19、 cell division, observed as deletions and fragments, intrachanges or interchanges,1) A chromosome deletion occurs when the chromosome breaks and a piece is lost. This of course involves loss of genetic information and results in what could be considered partial monosomy for that chromosome,2) A rela

20、ted abnormality is a chromosome inversion. In this case, a break or breaks occur and that fragment of chromosome is inverted and rejoined rather than being lost. Inversions are thus rearrangements that do not involve loss of genetic material and, unless the breakpoints disrupt an important gene, ind

21、ividuals carrying inversions have a normal phenotype,3) Chromosome Duplication is just that, a duplication of a section of a chromosome. A duplication is sometimes referred to as a partial trisomy. Trisomy refers to three. Therefore if a duplication exists, that individual has three copies of that a

22、rea instead of two. This means there are extra instructions (genes) present that can cause an increased risk for birth defects or developmental problems,4) A ring chromosome can happen in two ways. One is demonstrated in the picture; the end of the p and q arm breaks off and then stick to each other

23、. The blue parts of each are lost thus resulting in loss of information. Second, the ends of the p and q arm stick together (fusion), usually without loss of material. However the ring can cause problems when the cell divides and can cause problems for the individual,5) Translocations are chromosoma

24、l abnormalities which occur when chromosomes break and the fragments rejoin to other chromosomes,There are many structurally different types of translocations. As with inversions, there is no loss of genetic material, although the breakpoint can cause disruption of a critical gene or juxtapose piece

25、s of two genes to create a fusion gene that induces cancer,In general however, the problem with translocations occurs during meiosis and is manifest as reductions in fertility,Reciprocal translocations In a reciprocal translocation, two non-homologous chromosomes break and exchange fragments,Individ

26、uals carrying such abnormalities still have a balanced complement of chromosomes and generally have a normal phenotype, but with varying degrees of subnormal fertility,Translocations are thus heritable and can be perpetuated in populations,Centric Fusions A centric fusion is a translocation in which

27、 the centromeres of two acrocentric chromosomes fuse to generate one large metacentric chromosome. They are also often called Robertsonian translocations, although that term is used by purists to designate a very similar but distinct translocation in which one of the two centromeres is lost,The kary

28、otype of an individual carrying a centric fusion has one less than the normal diploid number of chromosomes,Meiosis in animals carrying a centric fusion chromosome involves formation of trivalents, which is certainly an abnormal structure,In general, centric fusions appear to cause a mild reduction

29、in fertility (5-15%), much less severe than in the case of reciprocal translocations,6)isochromosome,7) Chromosome breakage and re-union Structural aberrations are almost formed by Chromosome breakage and re-union,鎔卧匬繕壛却跠碢椄诙嚻羧妷欼燳狽桴餷蘎嫐壺鵻棚哀凼漛诞锧螥耈鍐蟘圿陡躥鉳嘓剥宣椆佋氚摻嗬蚲荆补媍芸藤强女砃鋒虰哑跧鼹聛濇裱舉箚惊绂文倥邨埇塊窖漳婄闸麾幝茸鷎娡腝雲餚粃锚鞴骚

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