【基础医学】10人类染色体畸变ENG V

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. fact

2、ors 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 alt

3、er cellular 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

4、aberrations 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 con

5、trolled 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

6、informative 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

7、 instability 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

8、 a change in 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 th

9、e haploid chromosome 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

10、from euploidy, although 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 s

11、uch individuals usually 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 monosom

12、y, also known as Turners 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. Triso

13、my is a specific instance 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

14、 (3 haploid sets of 23). 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

15、 birth is almost certainly 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 opposi

16、te poles, that is two chromosomes 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 pa

17、irs both travel into the same 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 chromati

18、ds will not separate and thus travel 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

19、examination of the metaphase stage of 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

20、 monosomy for that chromosome. (2) A related 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 b

21、reakpoints disrupt an important gene, individuals 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,

22、 that individual has three copies of that area 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

23、q arm breaks off and then stick to each other. 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 th

24、e individual. (5) Translocations are chromosomal 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

25、disruption of a critical gene or juxtapose pieces 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-homologou

26、s chromosomes break and exchange fragments. Individuals 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

27、 Fusions A centric fusion is a translocation in which 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

28、 in which one of the two centromeres is lost. The karyotype 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 ge

29、neral, centric fusions appear to cause a mild reduction 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

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