1、第四章第四章 人类染色体和染色体病人类染色体和染色体病医学遗传学人类染色体与染色体病1Dark Ages医学遗传学人类染色体与染色体病2Hypotonic PeriodDark Ages医学遗传学人类染色体与染色体病3Trisomy PeriodHypotonic PeriodDark Ages医学遗传学人类染色体与染色体病4Banding EraHypotonic PeriodDark AgesTrisomy Period医学遗传学人类染色体与染色体病5Molecular EraHypotonic PeriodDark AgesBanding EraTrisomy Period医学遗传学人类
2、染色体与染色体病6Denver SystemThe 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：核型：一个体细胞中的全部染色体，按其大一个体细胞中的全部染色体，按其大 小、形态特征顺序排列所构成的图像。小、形态特征顺序排列所构成的图像。医学遗传学人类染色体与染色体病7Chromosome can be distinguished by t
3、he 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与染色体病8Karyotype analysis:arranging the chromosomes of a cell into a karyotype,then analysis and compare with Denver system.Denver SystemThe
4、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与染色体病9Denver System医学遗传学人类染色体与染色体病10Banding Pattern医学遗传学人类染色体与染色体病11Banding Pattern医学遗传学人类染色体与染色体病12医学遗传学人类染色体与染色体病13医学遗传学人类染色体与染色体病14医学遗传学人类
5、染色体与染色体病15医学遗传学人类染色体与染色体病16医学遗传学人类染色体与染色体病17医学遗传学人类染色体与染色体病18医学遗传学人类染色体与染色体病19医学遗传学人类染色体与染色体病20医学遗传学人类染色体与染色体病21医学遗传学人类染色体与染色体病22医学遗传学人类染色体与染色体病23医学遗传学人类染色体与染色体病24医学遗传学人类染色体与染色体病25医学遗传学人类染色体与染色体病26医学遗传学人类染色体与染色体病27医学遗传学人类染色体与染色体病28医学遗传学人类染色体与染色体病29医学遗传学人类染色体与染色体病30医学遗传学人类染色体与染色体病31医学遗传学人类染色体与染色体病32X
6、染色体染色体Y染色体染色体13号染色体号染色体18号染色体号染色体21号染色体号染色体医学遗传学人类染色体与染色体病33医学遗传学人类染色体与染色体病34DNA fiber-FISH3 cosmid from MHC locus3540 Kb/cosmid医学遗传学人类染色体与染色体病35医学遗传学人类染色体与染色体病36Chromosome Painting医学遗传学人类染色体与染色体病37Chromosome Painting医学遗传学人类染色体与染色体病38Chromosome Painting医学遗传学人类染色体与染色体病39医学遗传学人类染色体与染色体病40CGH医学遗传学人类染色体
7、与染色体病41CGH医学遗传学人类染色体与染色体病42CGH医学遗传学人类染色体与染色体病43J Advantagesv Whole genome in 1 experimentv No need to culture tumor cellsv Sensitive detection of gene amplificationL Disadvantagesv Limited resolution(10 Mb del/dup)v Laboriousv Only gains and losses/no balanced rearrangementsv No information on the n
8、ature of the aberrationsv Retrospective analysisCGH医学遗传学人类染色体与染色体病44医学遗传学人类染色体与染色体病45医学遗传学人类染色体与染色体病46医学遗传学人类染色体与染色体病47医学遗传学人类染色体与染色体病48医学遗传学人类染色体与染色体病49医学遗传学人类染色体与染色体病50医学遗传学人类染色体与染色体病51医学遗传学人类染色体与染色体病52医学遗传学人类染色体与染色体病53医学遗传学人类染色体与染色体病54医学遗传学人类染色体与染色体病55Numerical Abnormality医学遗传学人类染色体与染色体病56Numeric
9、al Abnormality医学遗传学人类染色体与染色体病57Numerical Abnormality医学遗传学人类染色体与染色体病58Numerical Abnormality医学遗传学人类染色体与染色体病59Meiosis in animals.医学遗传学人类染色体与染色体病60医学遗传学人类染色体与染色体病612N2NN NN N1 1N N1 12N2N1 12N2N1 12N2N1 12N2N1 1N N1 1N N1 1N N1 1N N1 12N2N2N2N2N2N1 12N2N1 12N2NN NN NN NN NN N1 1N N1 1医学遗传学人类染色体与染色体病62Pr
10、imary non-disjunctionPrimary non-disjunction is the failure of chromosomes or 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-disjunctionTrisomy offspring arise from segregation at meiosis of an already-t
11、risomy parent.医学遗传学人类染色体与染色体病632N+12N+1N N2N2N2N2N2N2N1 12N2N1 1N NN N1 1N NN NN N1 1N N1 1医学遗传学人类染色体与染色体病64Numerical Abnormality医学遗传学人类染色体与染色体病65Mitosis in animal cells.医学遗传学人类染色体与染色体病662N2N2N2N2N2N2N2N2N2N2N2N1 12N2N1 12N2N2N2N1 12N2N1 147/45 Mosaic46/47/45 Mosaic医学遗传学人类染色体与染色体病67Numerical Abnorma
12、lity医学遗传学人类染色体与染色体病68The 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与染色体病69The Breakage and the Rejoin after breakage are the basis of chromoso
13、mal structural aberration.Chromosomal rearrangementRearrangement chromosomeStructural Aberration医学遗传学人类染色体与染色体病70Structural Aberration医学遗传学人类染色体与染色体病71Structural Aberration医学遗传学人类染色体与染色体病72Structural Aberration医学遗传学人类染色体与染色体病73Structural Aberration医学遗传学人类染色体与染色体病74Structural Aberration医学遗传学人类染色体与染色体
14、病75Structural Aberration医学遗传学人类染色体与染色体病76Inversion loopStructural Aberration医学遗传学人类染色体与染色体病77Structural Aberration医学遗传学人类染色体与染色体病78Inversion loopStructural Aberration医学遗传学人类染色体与染色体病79Structural Aberration医学遗传学人类染色体与染色体病80Structural Aberration医学遗传学人类染色体与染色体病81Structural Aberration医学遗传学人类染色体与染色体病82Str
15、uctural Aberration医学遗传学人类染色体与染色体病83Structural Aberration医学遗传学人类染色体与染色体病84Structural Aberration医学遗传学人类染色体与染色体病85Structural Aberration医学遗传学人类染色体与染色体病86ABCDStructural Aberration医学遗传学人类染色体与染色体病87Structural Aberration医学遗传学人类染色体与染色体病88Structural Aberration医学遗传学人类染色体与染色体病89Structural Aberration医学遗传学人类染色体与染
16、色体病90Structural Aberration医学遗传学人类染色体与染色体病91Structural Aberration医学遗传学人类染色体与染色体病92Structural Aberration医学遗传学人类染色体与染色体病93Structural Aberration6q2211p15医学遗传学人类染色体与染色体病94Structural Aberration医学遗传学人类染色体与染色体病95Structural Aberration医学遗传学人类染色体与染色体病96Chromosome Disease in ClinicalClinical featureThe general
17、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与染色体病97(trisomy 21 syndrome)Chromosome Disease in Clinica
18、l医学遗传学人类染色体与染色体病98oGrowth retardationoVarying degrees of mental retardationoFlattened face oUpward slanting of the eyes with epicanthal folds(内眦赘皮内眦赘皮)1 in 600 800 newbornsChromosome Disease in Clinical(trisomy 21 syndrome)医学遗传学人类染色体与染色体病991.Trisomy 95%,47,XX(XY),21Caused by non-disjunction of chrom
19、osome 21,correlated with age of mother.Chromosome Disease in Clinical(trisomy 21 syndrome)医学遗传学人类染色体与染色体病100医学遗传学人类染色体与染色体病101医学遗传学人类染色体与染色体病102Karyotype of affected：46,XX(XY),14,t(14q21q)2.Mosaic 2%4%,46/473.Unbalance translocationKaryotype of balance carrier：45,XX(XY),14,21,t(14q21q)Chromosome Dis
20、ease in Clinical1.Trisomy 92.5%,47,XX(XY),21(trisomy 21 syndrome)医学遗传学人类染色体与染色体病103医学遗传学人类染色体与染色体病104医学遗传学人类染色体与染色体病105医学遗传学人类染色体与染色体病1061 in 3500 8000 newborns(trisomy 18 syndrome)oGrowth retardationoMental retardationoCongenital heart diseaseoRocker-bottom feet ofixed flexion deformity of the fing
21、ers Chromosome Disease in Clinical医学遗传学人类染色体与染色体病107Chromosome Disease in Clinical1 in 3500 8000 newborns(trisomy 18 syndrome)医学遗传学人类染色体与染色体病108医学遗传学人类染色体与染色体病1091 in 25 000 newborns(trisomy 13 syndrome)oVarying degrees of mental retardationoCleft lip&Cleft palateoPolydactyly(postaxial)oEquinovarusC
22、hromosome Disease in Clinical医学遗传学人类染色体与染色体病110医学遗传学人类染色体与染色体病1111 in 50000 newborns(Cat Cry syndrome)Chromosome Disease in Clinical医学遗传学人类染色体与染色体病112医学遗传学人类染色体与染色体病113(45,X)1 in 5000 liveborn femalesChromosome Disease in Clinical医学遗传学人类染色体与染色体病114医学遗传学人类染色体与染色体病115Trisomy X syndrome(47,XXX)1 in 100
23、0 liveborn females1 in 250 psychopath of femalesTwo of the three X chromosomes are inactivated.Chromosome Disease in Clinical医学遗传学人类染色体与染色体病116医学遗传学人类染色体与染色体病1171 2 in 1000 malesoTall with disproportionately long arms/legsKlinefelter syndrome(47,XXY)1 in 100 mentally retarded males1 in 10 infertile
24、malesoPoorly developed secondary sex characteristicsoTesticular dysgenesisChromosome Disease in Clinical医学遗传学人类染色体与染色体病118医学遗传学人类染色体与染色体病1191 in 900 malesoTall statureXYY syndrome(47,XYY)1 in 30 male prison populations oPredisposition to violent,criminal behavior180 cm:1/200190 cm:1/30200 cm:1/10Chr
25、omosome Disease in Clinical医学遗传学人类染色体与染色体病120医学遗传学人类染色体与染色体病1211 in 1250 malesFragile X chromosome syndrome(Fra X)oShow mild to severe mental retardationoLarge,protruding earsoEnlarged testesoNarrow face with a prominent chinoBehavioral problemsChromosome Disease in Clinical医学遗传学人类染色体与染色体病122医学遗传学人类染色体与染色体病123医学遗传学人类染色体与染色体病124
