医学遗传学人类染色体和染色体病专家讲座.pptx

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,第四章,人类染色体和染色体病,医学遗传学人类染色体和染色体病,第1页,Painter TS,.Studies in mammalian spermatogenesis.II.The spermatogenesis of man.,J Exp Zool,.1923;37:291-336,Dark Ages,医学遗传学人类染色体和染色体病,第2页,Hsu TC,.Mammalian chromosomes in vitro.I.The karyotype of man.,J Hered,.1952;43:167-172,Tjio JH,Levan A,.The chromosome number of man.,Am J Obstet Gynecol,.1956;130:723-724,Hypotonic Period,Dark Ages,医学遗传学人类染色体和染色体病,第3页,Trisomy Period,Lejeune J,et al.Etude des chromosomes somatiques de neuf enfants mongoliens.,G.R.Acad.Sciences,.1959;2481721-1722,Ford CE,et al.A sex chromosomal anomaly in a case of gonadal dysgenesis(Turners syndrome).,Lancet,.1959;1:711-713,Jacob PA,et al.A case of human intersexuality having a possible XXY sex determining mechanism.,Nature,.1959;183:302-303.,Hypotonic Period,Dark Ages,医学遗传学人类染色体和染色体病,第4页,Banding Era,Caspersson T,et al.Differential banding of alkylating fluorochromes in human chromosomes.,Exp Cell Res,.1970;60:315-319,Hypotonic Period,Dark Ages,Trisomy Period,医学遗传学人类染色体和染色体病,第5页,Molecular Era,Pardue ML,et al.Molecular hybridization of radioactive DNA to the DNA of cytological preparations.,Proc.Natl.Acad.Sci.USA.,1969;64:600-604,Pinkel D,et al.Cytogenetic analysis using quantitative,high-sensitivity,fluorescence hybridization.,Proc.Natl.Acad.Sci.USA.,1986;83:2934-2938.,Hypotonic Period,Dark Ages,Banding Era,Trisomy Period,医学遗传学人类染色体和染色体病,第6页,Denver System,The,karyotype,is a photograph of all of the chromosomes of an individual cell;the term covers the number,relative sizes and structure of the chromosomes.,核型：,一个体细胞中全部染色体，按其大,小、形态特征次序排列所组成图像。,医学遗传学人类染色体和染色体病,第7页,Chromosome can be distinguished by the,relative sizes and,the position of the centromere.,Metacentric,(1,3,16,19,20),Submetacentric,(2,4-12,17,18,X),Acrocentric,(13,14,15,21,22,Y),Denver System,医学遗传学人类染色体和染色体病,第8页,Karyotype analysis:,arranging the chromosomes of a cell into a karyotype,then analysis and compare with,Denver system,.,Denver System,The,karyotype,is a photograph of all of the chromosomes of an individual cell;the term covers the number,relative sizes and structure of the chromosomes.,医学遗传学人类染色体和染色体病,第9页,Denver System,医学遗传学人类染色体和染色体病,第10页,Banding Pattern,Band,（带）,:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,Banding pattern,（带型）：,treated with chemical dyes,24 types of chromosomes appear its unique striations individually.,医学遗传学人类染色体和染色体病,第11页,Q-banding,：,QM,Banding Pattern,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第12页,医学遗传学人类染色体和染色体病,第13页,Q-banding,：,QM,G-banding,：,pancreatin,Giemsa,Banding Pattern,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第14页,医学遗传学人类染色体和染色体病,第15页,R-banding,：,treated specimen,Giemsa or A,cridine Orange,Banding Pattern,Q-banding,：,QM,G-banding,：,pancreatin,Giemsa,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第16页,医学遗传学人类染色体和染色体病,第17页,医学遗传学人类染色体和染色体病,第18页,C-banding,：,Y chromosome,centromere,secondary constriction,Banding Pattern,R-banding,：,treated specimen,Giemsa or A,cridine Orange,Q-banding,：,QM,G-banding,：,pancreatin,Giemsa,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第19页,医学遗传学人类染色体和染色体病,第20页,医学遗传学人类染色体和染色体病,第21页,T-banding,：,ending of chromosome,Banding PatternC-banding,：,Y chromosome,centromere,secondary constriction,R-banding,：,treated specimen,Giemsa or A,cridine Orange,Q-banding,：,QM,G-banding,：,pancreatin,Giemsa,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第22页,医学遗传学人类染色体和染色体病,第23页,N-banding,：,AgNO,3,Giemsa,NOR,T-banding,：,ending of chromosome,Banding Pattern,C-banding,：,Y chromosome,centromere,secondary constriction,R-banding,：,treated specimen,Giemsa or A,cridine Orange,Q-banding,：,QM,G-banding,：,pancreatin,Giemsa,Band:,treated with chemical dyes,the chromosome will appear as a series of alternate dark and light striations.,医学遗传学人类染色体和染色体病,第24页,医学遗传学人类染色体和染色体病,第25页,Landmark,Xp,Xq,Region,Band,1,1,2,2,1,2,3,4,5,6,7,8,Xq28,Banding Pattern,医学遗传学人类染色体和染色体病,第26页,Development,1.High resolution banding chromosome(HRBC),医学遗传学人类染色体和染色体病,第27页,医学遗传学人类染色体和染色体病,第28页,FISH,(fluorescence in situ hybridization),3.Molecular cytogenetics,Development,2.Microcytogenetics,1.High resolution banding chromosome(HRBC),医学遗传学人类染色体和染色体病,第29页,FISH,医学遗传学人类染色体和染色体病,第30页,FISH,医学遗传学人类染色体和染色体病,第31页,FISH,医学遗传学人类染色体和染色体病,第32页,X,染色体,Y,染色体,13,号染色体,18,号染色体,21,号染色体,FISH,医学遗传学人类染色体和染色体病,第33页FISH,(fluorescence in situ hybridization),DNA fiber-FISH,3.Molecular cytogenetics,Development,2.Microcytogenetics,1.High resolution banding chromosome(HRBC),医学遗传学人类染色体和染色体病,第34页,DNA fiber-FISH,3 cosmid from MHC locus,35,40 Kb/cosmid,医学遗传学人类染色体和染色体病,第35页,FISH,(fluorescence in situ hybridization),DNA fiber-FISH,Chromosome Painting,3.Molecular cytogenetics,Development,2.Microcytogenetics,1.High resolution banding chromosome(HRBC),医学遗传学人类染色体和染色体病,第36页,Chromosome Painting,医学遗传学人类染色体和染色体病,第37页,Chromosome Painting,医学遗传学人类染色体和染色体病,第38页,Chromosome Painting,医学遗传学人类染色体和染色体病,第39页,FISH,(fluorescence in situ hybridization),DNA fiber-FISH,Chromosome Painting,CGH,(comparative genomic hybridization),3.Molecular cytogenetics,Development,2.Microcytogenetics,1.High resolution banding chromosome(HRBC),医学遗传学人类染色体和染色体病,第40页,CGH,医学遗传学人类染色体和染色体病,第41页,CGH,医学遗传学人类染色体和染色体病,第42页,CGH,医学遗传学人类染色体和染色体病,第43页,Advantages,Whole genome in 1 experiment,No need to culture tumor cells,Sensitive detection of gene amplification,Disadvantages,Limited resolution(10 Mb del/dup),Laborious,Only gains and losses/no balanced rearrangements,No information on the nature of the aberrations,Retrospective analysis,CGH,医学遗传学人类染色体和染色体病,第44页,Heteromorphism,Banding pattern polymorphism,Chromosome heteromorphisms are normal variations in the appearance of chromosomes.,Be inherited in a Mendelian fashion,Constitutive heterochromatin,Not chromosomal abnormality in clinical,医学遗传学人类染色体和染色体病,第45页,Heteromorphism,Banding pattern polymorphism,Chromosomal length,Satellite,Secondary constriction,Polymorphism of Q,G,C banding,医学遗传学人类染色体和染色体病,第46页,Chromosomal Aberration,Numerical Abnormality,Structural Aberration,医学遗传学人类染色体和染色体病,第47页,Numerical Abnormality,单倍体,:,22+X,22+Y,二倍体,:,44+XX,44+XY,医学遗传学人类染色体和染色体病,第48页,Numerical Abnormality,Variation in chromosome number can take 2 forms:,整倍体,:,that which involves,whole sets,(genomes)of chromosomes,非,整倍体,:,the chromosome number is,not,an exact multiple of the haploid,（,单倍体,）,number,医学遗传学人类染色体和染色体病,第49页,整倍体,三倍体,:,the cell which has 3 sets(genomes)of chromosomes,3n 69,Numerical Abnormality,医学遗传学人类染色体和染色体病,第50页,Numerical Abnormality,整倍体,三倍体,:,the cell which has 3 sets(genomes)of chromosomes,3n 69,Tripolar spindle,医学遗传学人类染色体和染色体病,第51页,双雄受精,:,fertilization of 1 oocyte by 2 spermatozoa,双雌受精,:,non-expulsion of the 2nd polar body,Numerical Abnormality,整倍体,三倍体,:,the cell which has 3 sets(genomes)of chromosomes,3n 69,医学遗传学人类染色体和染色体病,第52页,整倍体,多倍体,四倍体,:,the cell which has 4 sets(genomes)of chromosomes,4n 92,核内复制,Numerical Abnormality,医学遗传学人类染色体和染色体病,第53页,核内复制,双分染色体,医学遗传学人类染色体和染色体病,第54页,Diplochromosome,整倍体,多倍体,四倍体,:,the cell which has 4 sets(genomes)of chromosomes,4n 92,核内复制,Numerical Abnormality,核内有丝分裂,医学遗传学人类染色体和染色体病,第55页,Be,found more commonly than,Euploid(,整倍体,),亚二倍体,:,less than the normal 2n number of chromosomes,Numerical Abnormality,非整倍体,超二倍体,:,more than the normal 2n number of chromosomes,医学遗传学人类染色体和染色体病,第56页,单体型,:,is the presence of only one copy of any chromosome,Loss of autosomes is not tolerated,Turner syndrome:45,X,Numerical Abnormality,非整倍体,亚二倍体,医学遗传学人类染色体和染色体病,第57页,Be found more commonly than,Monosomy,Trisomy,of sex chromosome is more commonly,Numerical Abnormality,非整倍体,超二倍体,三体型,:,is the presence of only three copy of any chromosome,医学遗传学人类染色体和染色体病,第58页,Meiotic(,减数分裂,)non-disjunction,Mitotic(,有丝分裂,)non-disjunction,Chromosome non-disjunction,Numerical Abnormality,Mechanism of,Aneuploid(,非整倍体,),医学遗传学人类染色体和染色体病,第59页,Meiosis in animals.,医学遗传学人类染色体和染色体病,第60页,Meiotic Non-Disjunction,Meiotic non-disjunction,arises from failure of paired homologous chromosomes or,sister chromatid,to disjoin at meiotic anaphase.,医学遗传学人类染色体和染色体病,第61页,Meiotic Non-Disjunction,2N,N,N,1,N,1,2N,1,2N,1,2N,1,2N,1,N,1,N,1,N,1,N,1,2N,2N,2N,1,2N,1,2N,N,N,N,N,N,1,N,1,医学遗传学人类染色体和染色体病,第62页,Primary non-disjunction,Primary non-disjunction,is the failure of chromosomes or,sister chromatid,to separate in meiosis.The,gamete,thus has two copies of a chromosome.Fertilization adds another copy to give a total of 3 copies.,Secondary non-disjunction,Trisomy offspring,arise from segregation at meiosis of an already-,trisomy,parent,.,Meiotic Non-Disjunction,医学遗传学人类染色体和染色体病,第63页,Meiotic Non-Disjunction2N+1,N,2N,2N,2N,1,2N,1,N,N,1,N,N,N,1,N,1,医学遗传学人类染色体和染色体病,第64页,Meiotic non-disjunction,Mitotic non-disjunction,Chromosome non-disjunction,Numerical Abnormality,Mechanism of,Aneuploid,医学遗传学人类染色体和染色体病,第65页,Mitosis in animal cells.,医学遗传学人类染色体和染色体病,第66页,Mitotic Non-Disjunction,Mitotic non-disjunction,arises from failure of sister chromatids to disjoin at mitotic anaphase.,2N,2N,2N,2N,2N,2N,1,2N,1,2N,2N,1,2N,1,47/45 Mosaic,46/47/45 Mosaic,医学遗传学人类染色体和染色体病,第67页,Meiotic non-disjunction,Mitotic non-disjunction,Chromosome non-disjunction,Chromosome loss,Numerical Abnormality,Mechanism of,Aneuploid,医学遗传学人类染色体和染色体病,第68页,The causality where a chromosome is missing from the new cell created via cell division.,Anaphase lag(,染色体分裂后期延滞,),may be due to delayed movement of a chromosome at anaphase.,Chromosome Loss,医学遗传学人类染色体和染色体病,第69页,The Breakage,and the,Rejoin,after breakage are the basis of chromosomal structural aberration.,Chromosomal rearrangement,Rearrangement chromosome,Structural Aberration,医学遗传学人类染色体和染色体病,第70页,Terminal,Del,etion,Structural Aberration,4q27,医学遗传学人类染色体和染色体病,第71页,Interstitial,Del,etion,Structural Aberration,4q13,4q25,医学遗传学人类染色体和染色体病,第72页,Paracentric,Inv,ersion,Structural Aberration,4q13,4q24,医学遗传学人类染色体和染色体病,第73页,Pericentric,Inv,ersion,Structural Aberration,4p14,4q21,医学遗传学人类染色体和染色体病,第74页,Structural Aberration,Pericentric,Inv,ersion,医学遗传学人类染色体和染色体病,第75页,Structural Aberration,Pericentric,Inv,ersion,医学遗传学人类染色体和染色体病,第76页,Inversion loop,Structural Aberration,Pericentric,Inv,ersion,医学遗传学人类染色体和染色体病,第77页,Structural Aberration,Pericentric,Inv,ersion,医学遗传学人类染色体和染色体病,第78页,Inversion loop,Structural Aberration,Pericentric,Inv,ersion,医学遗传学人类染色体和染色体病,第79页,R,ing Chromosome,Structural Aberration,2q31,2p21,医学遗传学人类染色体和染色体病,第80页,R,ing Chromosome,Structural Aberration,2q31,2p21,p21,q31,医学遗传学人类染色体和染色体病,第81页,R,ing Chromosome,Structural Aberration,医学遗传学人类染色体和染色体病,第82页,R,ing Chromosome,Structural Aberration,医学遗传学人类染色体和染色体病,第83页,Reciprocal,T,ranslocation,Structural Aberration,4q25,20q12,医学遗传学人类染色体和染色体病,第84页,Structural Aberration,Reciprocal,T,ranslocation,医学遗传学人类染色体和染色体病,第85页,Structural Aberration,Reciprocal,T,ranslocation,医学遗传学人类染色体和染色体病,第86页,A,B,C,D,Four-way junction,Structural Aberration,Reciprocal,T,ranslocation,医学遗传学人类染色体和染色体病,第87页,Robertsonian,T,ranslocation,Structural Aberration,医学遗传学人类染色体和染色体病,第88页,Structural Aberration,Robertsonian,T,ranslocation,医学遗传学人类染色体和染色体病,第89页,Whole Arm,T,ranslocation,Structural Aberration,医学遗传学人类染色体和染色体病,第90页,Complex,T,ranslocation,Structural Aberration,医学遗传学人类染色体和染色体病,第91页,I,sochromosome,Structural Aberration,医学遗传学人类染色体和染色体病,第92页,I,sochromosome,Structural Aberration,医学遗传学人类染色体和染色体病,第93页,Dic,entric Chromosome,Structural Aberration,6q22,11p15,医学遗传学人类染色体和染色体病,第94页,Dir,ect,Ins,ertion,Structural Aberration,医学遗传学人类染色体和染色体病,第95页,Inv,erse,Ins,ertion,Structural Aberration,医学遗传学人类染色体和染色体病,第96页,Chromosome Disease in Clinical,Clinical feature,The general features in autosome abnormalities are a triad of,growth retardation,mental retardation,and,specific somatic abnormalities.,Change of,sex chromosome,also have the abnormalities and malformations of internal or external genital organs.,医学遗传学人类染色体和染色体病,第97页,Down Syndrome,(trisomy 21 syndrome),Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第98页,Characteristics,Growth retardation,Varying degrees of mental retardation,Flattened face,Upward slanting of the eyes with,epicanthal folds(,内眦赘皮,),1 in 600 800 newborns,Chromosome Disease in Clinical,Down Syndrome,(trisomy 21 syndrome),医学遗传学人类染色体和染色体病,第99页,1.,Trisomy,95%,47,XX(XY),21,Caused by non-disjunction of chromosome 21,correlated with age of mother.,Chromosome Disease in Clinical,Down Syndrome,(trisomy 21 syndrome),医学遗传学人类染色体和染色体病,第100页,医学遗传学人类染色体和染色体病,第101页,医学遗传学人类染色体和染色体病,第102页,Karyotype of affected,：,46,XX(XY),14,t(14q21q),2.,Mosaic,2%4%,46/47,3.,Unbalance translocation,Karyotype of balance carrier,：,45,XX(XY),14,21,t(14q21q),Chromosome Disease in Clinical,1.,Trisomy,92.5%,47,XX(XY),21,Down Syndrome,(trisomy 21 syndrome),医学遗传学人类染色体和染色体病,第103页,医学遗传学人类染色体和染色体病,第104页,医学遗传学人类染色体和染色体病,第105页,医学遗传学人类染色体和染色体病,第106页,1 in 3500 8000 newborns,Edwards Syndrome,(trisomy 18 syndrome),Characteristics,Growth retardation,Mental retardation,Congenital heart disease,Rocker-bottom feet,fixed flexion deformity of the fingers,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第107页,Chromosome Disease in Clinical,1 in 3500 8000 newborns,Edwards Syndrome,(trisomy 18 syndrome),医学遗传学人类染色体和染色体病,第108页,医学遗传学人类染色体和染色体病,第109页,1 in 25 000 newborns,Patau Syndrome,(trisomy 13 syndrome),Characteristics,Varying degrees of mental retardation,Cleft lip&Cleft palate,Polydactyly(postaxial),Equinovarus,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第110页,医学遗传学人类染色体和染色体病,第111页,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,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第112页,医学遗传学人类染色体和染色体病,第113页,Turner Syndrome,(45,X),1,in 5000,liveborn females,Characteristics,Short stature&,Webbed neck,Ovarian dysgenesis,primary amenorrhea,infertility,Absence of secondary sex characteristics,Underdeveloped breasts;wide nipples,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第114页,医学遗传学人类染色体和染色体病,第115页,Trisomy X syndrome(47,XXX),1 in 1000,liveborn females,1 in 250 psychopath,of females,Two of the three X chromosomes are inactivated.,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第116页,医学遗传学人类染色体和染色体病,第117页,1,2 in 1000 males,Tall with disproportionately long arms/legs,Klinefelter syndrome(47,XXY),1,in 100,mentally retarded males,1 in 10,infertile,males,Poorly developed secondary sex characteristics,Testicular dysgenesis,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第118页,医学遗传学人类染色体和染色体病,第119页,1 in 900 males,Tall stature,XYY syndrome(47,XYY),1,in 30,male prison populations,Predisposition to violent,criminal behavior,180 cm:1/200,190 cm:1/30,200 cm:1/10,Chromosome Disease in Clinical,医学遗传学人类染色体和染色体病,第120页,医学遗传学人类染色体和染色体病,第121页,1 in 1250 males,Fra