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1、Post-Translation Processing,Post-translational modifications:肽链从核蛋白体释放后，经过细胞内各种修饰处理成为有活性的成熟蛋白质的过程。 Primary translation product is folded and bonded into a specific three-dimensional structure. Two or more polypeptide chains combine to form a single mature protein complex. Cleavage of the protein The
2、 protein products may also be modified chemically,STRUCTURE OF HUMAN CHROMOSOMES,Composition of Chromatin DNA Proteins (histones and nonhistone) The basic structure unit of chromatin: NucleosomeH1, (H2A, H2B, H3, H4)2,(H2A,H2B,H3,H4),ORGANIZATION OF THE HUMAN GENOME,Single-copy or unique DNARepetiti
3、ve DNA,Single-Copy DNA Sequences,Once or a few times /a genomeShort stretches (several kb)Coding portion of genes: a small proportion of all the single-copy DNA,Repetitive DNA Families,DefinitionHundreds to millions of times in the genomeRoleMaintain chromosome structureCategory Clustered repeated s
4、equences Dispersed repeated sequences,Principles of Clinical Cytogenetics,Yuxia YangDepartment of Medical Genetics, Peking University Health Science Center,Key Points,Introduction,Karyotype,Classification of Human Chromosome,Human Chromosome Identification,CategoriesDefinitionsMechanisms,Chromosome
5、Abnormalities,Introduction to Cytogenetics,Clinical indications for chromasome analysis,Cytogenetics: the study of chromosomes and their abnormalities is called cytogenetics.,The Human Karyotype,The chromosomes are classified into 7 groups (A-G),Karyotype：是指一个体细胞中的全部染色体，按照大小、形态特征顺序排列所构成的图像,Centromer
6、e (primary constriction) 、p (short arm) 、 q (long arm),G banding,A chromosome at metaphase,Classification of Human Chromosomes,A Normal male Karyotype: 46,XY,Chromosome Identification,Identification of Human Chromosomes stainedA uniform system of chromosome classification ISCN (An International Syst
7、em for Human Cytogenetic Nomenclature),Chromosome Identification,G Banding: trypsin(胰蛋白酶) 、 Giemsa(姬姆萨)Q Banding: quinacrine mustard(喹吖因氮芥) R Banding: special treatmemt (heating) 、 staining 、 the reverse of G or Q banding,G Banding,Q Banding,R banding,Ideogram showing G banding patterns for human ch
8、romosomes at metaphase,Chromosome Identification,Identification of Human Chromosomes stainedA uniform system of chromosome classification ISCN (An International System for Human Cytogenetic Nomenclature),ISCN规定的界标：着丝粒、端粒、明显的带,Arm Region Band Sub-band,Xq13,Chromosome Identification,C Banding: stainin
9、g the centromeric region、 other constitutive heterochromatin regionsHigh-Resolution Banding: chromosomes stained at the stage of prophase or prometaphase, detecting a subtle structural abnormality(前中期、晚前期的单倍染色体带纹数可达550-850条带;典型中期染色体，一套单倍染色体带纹数约320-400条带 ),C Banding,High-Resolution Banding,Fluorescen
10、ce In Situ Hybridization (FISH:荧光原位杂交),Principles: Labeling probe with a fluorescent dyeDenature of the probe and metaphase、prophase or interphase chromosomesHybridizationVisualizing the location of hybridization under a fluorescence microscope,Chromosome Identification,Probes: three types gene-spec
11、ific or locus-specific probes, repetitive DNA probes (satellite DNA probes) chromosome painting probes (probes for entire chromosomes or chromosome arms) one-color, two-color, three-color, multicolor,Spectral karyotyping (SKY：光谱核型分析),Application: to examine the presence or absence of a particular DN
12、A sequence to diagnose the existence of an abnormal chromosome number in clinical materialto detect chromosome rearrangements with combinations of FISH probes,chromosome 18 aqua, X chromosome green, Y chromosome red,chromosome 18 aqua, X chromosome green,chromosome 13 green, chromosome 21 red,Prader
13、-Willi syndrome,demonstrating deletion of 15q11-q13,Green：alpha satellite DNA at the chromosome 15 centromere,Red：SNRPN gene,Chromosome Abnormalities,Abnormalities of Chromosome NumberAbnormalities of Chromosome Structure,Abnormalities of Chromosome Number,Euploid Variation：以染色体组为单位发生的染色体成倍的增减。Aneup
14、loid Variation：细胞内染色体数目增加或减少一条或几条。,Triploidy and Tetraploidy,Triploid(三倍体) Definition: 3n Reason: dispermy(双受精) (most common)、 digyny(双雌受精) Phenotypic expression: paternal-abnormal placenta; maternal-abortion,karyotypes: 69,XXX; 69,XXY; 69,XYY,Tetraploid(四倍体) Definition: 4n Reason: endoreduplication
15、 (核内复制), endomitosis (核内的有丝分裂) Karyotypes: 92,XXXX or 92,XXYY,Aneuploidy,Trisomy Definition: a trisomic cell involves a single extra chromosome; that is, the cell has three copies of a particular chromosomes and two copies of other chromosomes. A trisomic cell is 2n+1 Example: trisomy 21 (karyotype:
16、 47,XX/XY,+21),Monosomy Definition: a monosomic cell involves a loss of a single chromosome; that is, the cell is 2n-1. Example: Turner syndrome(Turner syndrome karyotype: 45, X),Mechanism Meiotic(减数分裂)nondisjunction (most common): the failure of a pair of chromosomes to disjoin properly during one of the two meiotic divisions, usually during meiosis I. The propensity of a chromosome pair to nondisjunction has been strongly associated with aberrations in the frequency or placement, or both, of recombination events in meiosis I.,
