1、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 are usually fatal or ill-adaptive,especially in animals
2、.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-type chromosome aberrations at the next mitosis.Such aberrati
3、ons can alter cellular phenotypes,and are important in various areas of biology:Medical Genetics Medical and public-health applications include perinatal diagnostics characterization of specific cancer types,carcinogenesis risk estimation,radiation biodosimetry and radiotherapeutic treatment plannin
4、g.Medical Genetics Analyzing chromosome 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 bre
5、aks(DSBs),and its timing can be controlled more accurately.Medical Genetics 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.Medical Genetics The spect
6、rum of different radiation-induced chromosome aberrations is informative about the geometry of chromosomes during interphase,and vice versa.Medical Genetics Chromosomal instability,in which new aberrations(though often not of the type characteristic of G0/G1 damage)continue to arise many generations
7、 after irradiation,represents a form of genomic instability,and genomic instability is prominent during neoplastic progression.Medical 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.Medi
8、cal 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(1)Euploidy is the condition of having a normal number of structurally normal chromosomes.Euploid human females have 4
9、6 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 Genetics(2)Aneuploidy is the condition of having less than or more than the normal diploid number of chromosomes,
10、and is the most frequently observed type of cytogenetic abnormality.In other words,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
11、 small deviation from euploidy for the simple reason that major deviations are 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 o
12、f 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 Turners syndrome.Monosomy is most commonly lethal during prenatal development.Medical Genetics Trisomy is having three chromosomes of a pa
13、rticular 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 instance of polysomy,a more general term that indicates having more than two of any given chromosome.Medical Genetics Another t
14、ype 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).Medical Genetics Production of triploids seems to be relatively common and can occur by,for example,fertilizat
15、ion by two sperm.Medical Genetics 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 a mosaic,having a large proportion of diploid cells.Medical Genetics(3)Chromoso
16、me 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 chromosomes or chromatids go to one pole and none to the other.Medical Geneti
17、cs 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.Medical Genetics In meiosis I,the error occurs when the homologous pairs both travel into the same daughter cell.The result is two daughte
18、r 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 Genetics In meiosis II,the error occurs when the sister chromatids will not separate and thus travel into t
19、he same daughter cell.Medical GeneticsNon-disjunction in Meiosis II:Medical GeneticsFertilization following Meiosis I error:Medical GeneticsFertilization following Meiosis II error:Medical GeneticsMedical GeneticsB.Chromosome Structural Aberration Structural aberration is a change in chromosome stru
20、cture detectable 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
21、results in what could be considered partial monosomy for that chromosome.Medical GeneticsMedical GeneticsMedical GeneticsMedical Genetics(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
22、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 normal phenotype.Medical GeneticsMedical GeneticsMedical GeneticsMedical GeneticsMedical Genetics(3)Chromosome Duplication
23、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 area instead of two.This means there are extra instructions(genes)present that can ca
24、use an increased risk for birth 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 res
25、ulting 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.Medical GeneticsMedical GeneticsMedical Genetics(5)Translocations are chromosom
26、al 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 breakpoint can cause disruption of a critical gene or
27、juxtapose pieces of two genes to create a fusion gene that induces cancer.Medical Genetics In general however,the problem with translocations occurs during meiosis and is manifest as reductions in fertility.Medical GeneticsReciprocal translocations In a reciprocal translocation,two non-homologous ch
28、romosomes 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 GeneticsMedical Genetics Trans
29、locations are thus heritable and can be perpetuated in populations.Medical GeneticsCentric 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,alth
30、ough that term is used by purists to designate a very similar but distinct translocation in which one of the two centromeres is lost.Medical Genetics The karyotype of an individual carrying a centric fusion has one less than the normal diploid number of chromosomes.Medical Genetics.Medical GeneticsM
31、edical Genetics Meiosis in animals carrying a centric fusion chromosome involves formation of trivalents,which is certainly an abnormal structure.Medical Genetics In general,centric fusions appear to cause a mild reduction in fertility(5-15%),much less severe than in the case of reciprocal translocations.Medical Genetics(6)isochromosomeMedical GeneticsMedical Genetics(7)Chromosome breakage and re-union Structural aberrations are almost formed by Chromosome breakage and re-union.Medical GeneticsMedical GeneticsMedical Genetics
