医学遗传学)11人类染色体畸变ppt课件

1、Medical Genetics末代沙皇尼古拉二世的公主斯塔西娅安娜-安德森1956电影真假公主Medical GeneticsMedical Genetics Any type of change in the chromosome structure or number (deficiencies, duplications, translocations, inversions, etc.). Medical Genetics Although it can be a mechanism for enhancing genetic diversity, such alterations

2、are usually fatal or ill-adaptive, especially in animals. Medical GeneticsA. Ionizing radiation Ionizing radiation produces rearrangements of the genome.Medical GeneticsMedical Genetics When irradiation occurs during the G0/G1 phase of the cell cycle, large-scale rearrangements appear as exchange-ty

3、pe chromosome aberrations at the next mitosis. Such aberrations can alter cellular phenotypes, and are important in various areas of biology:Medical Genetics Analyzing chromosome aberrations helps characterize repair/misrepair pathways involved in the processing of DNA damage. Ionizing radiation has

4、 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 controlled more accurately. Medical Genetics Moreover, initial radiation damage has a discrete, stochastic character that ca

5、n be modulated by using different kinds of radiation (e.g. a -particles versus x-rays) having different ionization densities.Medical Genetics The spectrum of different radiation-induced chromosome aberrations is informative about the geometry of chromosomes during interphase, and vice versa. Medical

6、 GeneticsB. chemical mutagen A kind of substances, such as drugs or toxins ,that causes chromosomal aberrations of living organisms, or increase the rate of mutation. Medical GeneticsDrugantitumor drug抗肿瘤药物抗肿瘤药物 环磷酰胺、氮芥、白硝安马利兰、环磷酰胺、氮芥、白硝安马利兰、甲氨喋呤、阿糖胞苷等抗癌药物甲氨喋呤、阿糖胞苷等抗癌药物Tocolysis子宫收缩抑制剂子宫收缩抑制剂drug wh

7、ich prevent pregnancy reaction(预防妊娠反响的药物预防妊娠反响的药物)anti-epileptic 苯妥英钠可引起人淋巴细胞多倍体细胞苯妥英钠可引起人淋巴细胞多倍体细胞数增高数增高 Medical Genetics agricultural chemicals Some agricultural chemicals can induce chromosome aberration, like phosphate pesticide.Medical Genetics Industrial poisons 苯、甲苯、铝、砷、二硫化碳、氯丁二稀、氯乙烯单体Medical

8、 Genetics Food additive Preservative(防腐剂),pigment(色素),AF-2(硝基呋喃基糖酰胺),benzosulfimide(环己基糖精)。Medical Genetics toxoid sterigmatocystin(杂色曲霉素), Flavacin(黄曲霉素), clavacin(棒曲霉素)等 virus German measles virus(风疹病毒), (hepatovirus)乙肝病毒, Measles virus(麻疹病毒), cytomegalovirus(巨细胞病毒)Medical Genetics Down综合征与母亲年龄Med

9、ical GeneticsA. chromosome numerical aberration Numerical aberration is a change in the number of chromosomes from the normal number characteristic of the human beings. Medical Genetics euploidchromosome numerical aberration aneupliod Medical Genetics(1) Euploidy is the condition of having a normal

10、number of structurally normal chromosomes. Euploid human females have 46 chromosomes (44 autosomes and two X chromosomes).Medical Genetics Polyploidy is a multiple of the haploid chromosome number (n) other than the diploid number (i.e., 3n, 4n and so on). Medical GeneticsTriploidy A triploid indivi

11、dual has three of every chromosome, that is, three haploid sets of chromosomes. A triploid human would have 69 chromosomes (3 haploid sets of 23). Medical Genetics Production of triploids seems to be relatively common and can occur by, for example, fertilization by two sperm. Medical GeneticsMedical

12、 Genetics Digyny(双雌受精) Dispermy(双雄受精) Endoreduplication核内复制 Endomitosis核内有丝分裂Medical GeneticsMedical Genetics(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,

13、 it is any deviation from euploidy, although many authors restrict use of this term to conditions in which only a small number of chromosomes are missing or added. Medical Genetics Generally, aneuploidy is recognized as a small deviation from euploidy for the simple reason that major deviations are

14、rarely compatible with survival, and such individuals usually die prenatally. Medical Genetics The two most commonly observed forms of aneuploidy are monosomy and trisomy.Medical Genetics Monosomy is lack of one of a pair of chromosomes. An individual having only one chromosome 6 is said to have mon

15、osomy 6. A common monosomy seen in many species is X chromosome monosomy, also known as Turners syndrome. Monosomy is most commonly lethal during prenatal development.Medical Genetics Trisomy is having three chromosomes of a particular type. A common autosomal trisomy in humans in Down syndrome, or

16、trisomy 21, in which a person has three instead of the normal two chromosome 21s. Trisomy is a specific instance of polysomy, a more general term that indicates having more than two of any given chromosome. Medical Genetics However, birth of a live triploid is extraordinarily rare and such individua

17、ls are quite abnormal. The rare triploid that survives for more than a few hours after birth is almost certainly a mosaic, having a large proportion of diploid cells. Medical Genetics(3) Chromosome non-disjunction The failure of a pair of homologous chromosomes to separate properly during meiosis. T

18、he failure of homologues (at meiosis) or sister chromatids (at mitosis) to separate properly to opposite poles, that is two chromosomes or chromatids go to one pole and none to the other. Medical Genetics Non-disjunction can occur during meiosis I or meiosis II. Medical Genetics In meiosis I, the er

19、ror occurs when the homologous pairs 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). Medical GeneticsNon-disjunction in Meiosis I: Medical

20、 Genetics In meiosis II, the error occurs when the sister chromatids will not separate and thus travel into the same daughter cell. 单体型单体型45,x45,xMedical GeneticsNon-disjunction in Meiosis II: Medical GeneticsFertilization following Meiosis I error: Medical GeneticsFertilization following Meiosis II

21、 error: Medical GeneticsMedical Genetics三体型三体型2121三体三体Medical Genetics Non-disjunction occurs during early period of merogenesis,the result is mosaicMedical Genetics Chromosome lossMedical GeneticsB. Chromosome Structural Aberration Structural aberration is a change in chromosome structure detectabl

22、e by microscopic examination of the metaphase stage of cell division, observed as deletions and fragments, intrachanges or interchanges. Medical Genetics(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

23、 what could be considered partial monosomy for that chromosome. Medical GeneticsMedical GeneticsMedical GeneticsMedical Genetics46,XX(XY),del(1)(q21)/ 46,XX(XY),del(1)(pterq21)46,XX(XY),del(3)(q21q31)/ 46,XX(XY),del(3)(pterq21:q31q31)Medical Genetics(2) A related abnormality is a chromosome inversio

24、n. 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, individuals carrying inversions have a norm

25、al phenotype. Medical GeneticsMedical GeneticsMedical GeneticsMedical GeneticsMedical Genetics46XX(XY),inv(1)(p22p34)/ 46XX(XY),inv(1)(pterp34:p22p34:p22qter)46XX(XY),inv(2)(p15q21)/ 46XX(XY),inv(2)(pterq15:q21p15:q21qter)Medical Genetics(3) Chromosome Duplication is just that, a duplication of a se

26、ction 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 area instead of two. This means there are extra instructions (genes) present that can cause an increased risk for b

27、irth defects or developmental problems. Medical GeneticsMedical GeneticsMedical Genetics(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. The blue parts of each are lost thus resulting in loss of info

28、rmation. 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. Medical GeneticsMedical GeneticsMedical Genetics46,XX(XY),r(2)(p21p31)/46,XX(XY),r(2)(p21p31)Me

29、dical Genetics(5) Translocations are chromosomal abnormalities which occur when chromosomes break and the fragments rejoin to other chromosomes. Medical Genetics There are many structurally different types of translocations. As with inversions, there is no loss of genetic material, although the brea

30、kpoint can cause disruption of a critical gene or juxtapose pieces of two genes to create a fusion gene that induces cancer. Medical GeneticsReciprocal translocations In a reciprocal translocation, two non-homologous chromosomes break and exchange fragments. Medical GeneticsMedical GeneticsMedical Genetics Individuals carrying such abnormalities still have a balanced complement of chromosomes and generally have a normal phenotype, but with varying degrees of subnormal fertility. Medical Genetics46,XX(XY),t(2;5)(q21:q31) /46,XX(XY),t(2;5)(2pter2q21:5q315qter;5pter5q31:2q212qter)M