医学遗传学-第四章人类染色体与染色体病ppt课件

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Dark AgesHypotonic PeriodDark AgesTrisomy PeriodHypotonic PeriodDark AgesBanding EraHypotonic PeriodDark AgesTrisomy PeriodMolecular EraHypotonic PeriodDark AgesBanding EraTrisomy PeriodDenver SystemThe karyotype is a photograph of all of the chromosomes of an individual c

2、ell; the term covers the number, relative sizes and structure of the chromosomes. 核型：一个体细胞中的全部染色体，按其大核型：一个体细胞中的全部染色体，按其大 小、形状特征顺序陈列所构成的图像。小、形状特征顺序陈列所构成的图像。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

3、, 18, X)Acrocentric(13, 14, 15, 21, 22, Y)Denver SystemKaryotype analysis: arranging the chromosomes of a cell into a karyotype, then analysis and compare with Denver system.Denver SystemThe karyotype is a photograph of all of the chromosomes of an individual cell; the term covers the number, relati

4、ve sizes and structure of the chromosomes. Denver SystemBanding PatternBanding PatternX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DNA fiber-FISH3 cosmid from MHC locus3540 Kb/cosmidChromosome PaintingChromosome PaintingChromosome PaintingCGHCGHCGHJ Advantagesv Whole genome in 1 experimentv No need t

5、o 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 nature of the aberrationsv Retrospective analysisCGHNumerical AbnormalityNumerical AbnormalityNumeri

6、cal AbnormalityNumerical AbnormalityMeiosis in animals.2N2NN 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 1Primary non-disjunctionPrimary non-disjunction is the failure of chromosomes or sister chromatid to separate in meiosis. The

7、 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-trisomy parent.2N+12N+1N N2N2N2N2N2N2N1 12N2N1 1N NN N1 1N NN NN N1 1N N1 1Numerical AbnormalityMitosis

8、in animal cells.2N2N2N2N2N2N2N2N2N2N2N2N1 12N2N1 12N2N2N2N1 12N2N1 147/45 Mosaic46/47/45 MosaicNumerical AbnormalityThe 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.Chr

9、omosome LossThe Breakage and the Rejoin after breakage are the basis of chromosomal structural aberration.Chromosomal rearrangementRearrangement chromosomeStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural Aberrati

10、onInversion loopStructural AberrationStructural AberrationInversion loopStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationABCDStructural AberrationStructural AberrationStructural Abe

11、rrationStructural AberrationStructural AberrationStructural AberrationStructural AberrationStructural Aberration6q2211p15Structural AberrationStructural AberrationChromosome Disease in ClinicalClinical featureThe general features in autosome abnormalities are a triad of growth retardation, mental re

12、tardation, and specific somatic abnormalities.Change of sex chromosome also have the abnormalities and malformations of internal or external genital organs.Chromosome Disease in ClinicaloGrowth retardationoVarying degrees of mental retardationoFlattened face oUpward slanting of the eyes with epicant

13、hal folds(内眦赘皮内眦赘皮)1 in 600 800 newbornsChromosome Disease in Clinical1. Trisomy 95%, 47, XX(XY), 21Caused by non-disjunction of chromosome 21, correlated with age of mother.Chromosome Disease in ClinicalKaryotype of affected：46, XX(XY), 14, t(14q21q)2. Mosaic 2% 4%, 46/473. Unbalance translocationK

14、aryotype of balance carrier：45, XX(XY), 14, 21, t (14q21q)Chromosome Disease in Clinical1. Trisomy 92.5%, 47, XX(XY), 211 in 3500 8000 newbornsoGrowth retardationoMental retardationoCongenital heart diseaseoRocker-bottom feet ofixed flexion deformity of the fingers Chromosome Disease in ClinicalChro

15、mosome Disease in Clinical1 in 3500 8000 newborns1 in 25 000 newbornsoVarying degrees of mental retardationoCleft lip & Cleft palateoPolydactyly (postaxial)oEquinovarusChromosome Disease in Clinical1 in 50000 newbornsChromosome Disease in Clinical1 in 5000 liveborn femalesChromosome Disease in C

16、linicalTrisomy X syndrome (47, XXX)1 in 1000 liveborn females1 in 250 psychopath of femalesTwo of the three X chromosomes are inactivated.Chromosome Disease in Clinical1 2 in 1000 malesoTall with disproportionately long arms/legsKlinefelter syndrome (47, XXY)1 in 100 mentally retarded males1 in 10 infertile malesoPoorly developed secondary sex characteristicsoTesticular dysgenesisChromosome Disease in Clinical1 in 900 malesoTall statureXYY syndrome (47, XYY)1 in 30 male prison populations oPredisposition to violent, criminal behavior180 cm: 1/20019