Cytogenetics Part 1 Dr. Mohammed Hussein M.B.Ch.B, MSC, PhD, DCH (UK), MRCPCH 5:00 AM

Numerical Chromosomal Abnormalities Introduction Numerical Chromosomal Abnormalities Structural Chromosomal Abnormalities Advances in Molecular Cytogenetics 5:00 AM

Introduction 5:00 AM

Chromosome abnormalities are: Seen in 1 /150 live births The leading known cause of mental retardation The leading known cause of pregnancy loss 50% of fetal losses during the first trimester of pregnancy 20% of fetuses lost during the second trimester of pregnancy 5:00 AM

Karyotyping 5:00 AM

Karyotyping Chromosomes are most easily visualized during the metaphase stage of mitosis, when they are maximally condensed They are photographed under the microscope to create a karyotype Karyotype is an ordered display of the 23 pairs of human chromosomes in a typical somatic cell 5:00 AM

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Karyogram Karyogram represents a drawing of each type of chromosome The presentation is haploid (only one copy of each chromosome is shown) 5:00 AM

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Chromosome Banding To visualize chromosomes in a karyotype, various stains are applied so that banding is evident G-banding: Mitotic chromosomes are partially digested with trypsin (to digest some associated protein) and then stained with Giemsa, a dye that binds DNA 5:00 AM

NOT X q twenty-two point one 2 2 .1 X q two-two point one NOT X q twenty-two point one 5:00 AM

Chromosome Nomenclature 5:00 AM

Metacentric chromosomes: have the centromere near the middle Submetacentric chromosomes: have the centromere displaced toward one end Acrocentric chromosomes: have the centromere far toward one end 5:00 AM

Acrocentric Chromosomes Have the centromere far toward one end Chromosomes 13, 14,15, 21, and 22 Only the acrocentric chromosomes are involved in Robertsonian translocations 5:00 AM

21, 22, 13 , 14 , 15 Mnemonic Acrocentric chromosomes 1,2,3,4,5 21, 22, 13 , 14 , 15 5:00 AM

Common Symbols Used in Karyotype Nomenclature 1-22 Autosome number X, Y Sex chromosomes (+) or (–) When placed before an autosomal number, indicates that chromosome is extra or missing p Short arm of the chromosome q Long arm of the chromosome t Translocation del Deletion inv Inversion i Isochromosome r Ring chromosome 5:00 AM

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46,XY 46,XX 47,XY,+21 47,XX,+13 45,XX, –13 47,XX,+18 47,XXY 45,X Normal male 46,XX Normal female 47,XY,+21 Male with extra chromosome no.21 (Trisomy 21) (Down syndrome) 47,XX,+13 Female with extra chromosome no.13 (Trisomy 13) (Patau syndrome) 45,XX, –13 Female with missing chromosome no.13 (Monosomy 13) 47,XX,+18 Female with extra chromosome no.18 (Trisomy 18) (Edward syndrome) 47,XXY Male with extra X chromosome (Klinefelter syndrome) 45,X Female with missing X chromosome (Turner syndrome) 46,XY,t(2p;8p) Male with translocation between short arms of chromosomes 2 & 8 46,XY, del(5p) Male with deletion in short arm of chromosome 5 (Cri Du Chat syndrome) 46,X,r(X) Female with ring chromosomes X (Turner syndrome) 5:00 AM

Chromosome Abnormalities Numerical Chromosomal Abnormalities Structural Chromosomal Abnormalities 5:00 AM

Numerical Chromosome Abnormalities Polidy : is the no. of the sets of chromosomes in the cell Euploid: When a cell has a multiple of 23 chromosomes, it is said to be euploid. Haploid: 1 set of 23 chromosome (gametes) Diploid: 2 sets of 23 chromosomes (46) (somatic cells) Triploidy: 3 sets of 23 chromosomes (69) Tetraploidy: 4 sets of 23 chromosomes (92) 5:00 AM

Triploidy 5:00 AM

Triploidy Result of the fertilization of an ovum by two sperm cells Is common at conception, but the vast majority of these conceptions are lost prenatally However, about 1 in 10,000 live births is a triploid These babies have multiple defects of the heart and central nervous system, and they do not survive 5:00 AM

Tetraploidy 5:00 AM

Tetraploidy This lethal condition is much rarer than triploidy among live births Only a few cases have been described 5:00 AM

Aneuploidy 5:00 AM

Aneuploidy Aneuploidy, a deviation from the euploid number, represents the gain (+) or loss (–) of a specific chromosome Two major forms of aneuploidy are observed: Monosomy (loss of a chromosome) (–) Trisomy (gain of a chromosome) (+) 5:00 AM

Aneuploidy Autosomal aneuploidy Sex chromosome aneuploidy Monosomy (–) Trisomy (+) Sex chromosome aneuploidy 5:00 AM

Autosomal aneuploidy 5:00 AM

Autosomal aneuploidy All autosomal monosomies are inconsistent with a live birth Only three autosomal trisomies are consistent with a live birth Trisomy 13 Trisomy 18 Trisomy 21 5:00 AM

Trisomy 13 (Patau Syndrome) 47 ,XX ,+13 47,XY,+13 or 47,XX,+13 5:00 AM

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Trisomy 18 (Edward Syndrome) 47 ,XY ,+18 47,XY,+18 or 47,XX,+18 5:00 AM

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Trisomy 21 (Down Syndrome) 47 ,XX ,+21 47,XY,+21 or 47,XX,+21 5:00 AM

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Sex chromosome aneuploidy 5:00 AM

Sex chromosome aneuploidy Relatively common Have less severe consequences than does autosomal aneuploidy. 5:00 AM

Some generalizations are helpful If a Y chromosome is present, the phenotype is male (regardless the no. of X ) 46,XY = Male 46,XX = Female 45,XO = Female (Turner) 47,XXY = Male ( Klinefelter) 5:00 AM

Some generalizations are helpful One X chromosome is required for survival and any other X will become a Barr body 46,XX = One Bar body 46,XY = No Bar body 45,XO = 47,XXY = 47,XXX = Tow Bar bodies 5:00 AM

Sex chromosome aneuploidies Extra X chromosome: Male with extra X = 47,XXY Female with extra X = 47,XXX Extra Y chromosome Male with extra Y = 47,XYY Missing X chromosome: Female with missing X = 45,X or 45,XO 5:00 AM

Klinefelter Syndrome 47 ,XXY 5:00 AM

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Turner Syndrome 45 ,X or 45,XO 5:00 AM

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Linda Hunt 5:00 AM

Triple X Syndrome 47 ,XXX 5:00 AM

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Other rare Sex chromosome aneuploidies: XXY Syndrome (47,XXY) XXYY Syndrome (48,XXYY) XXXX Syndrome (48,XXXX) or Tetrasomy X XXXXX Syndrome (49,XXXXX) or Pentasomy X 5:00 AM

Nondisjunction is the usual cause of aneuploidies 5:00 AM

Disjunction during Meiosis I Disjunction during Meiosis II 5:00 AM

Non-disjunction during Meiosis I Disjunction during Meiosis II 5:00 AM

Non-disjunction during Meiosis I Non-disjunction during Meiosis II 5:00 AM

Some important points to remember: Nondisjunction is the usual cause of aneuploidies including: Down syndrome (Trisomy 21) Edward syndrome (Trisomy 18) Patau syndrome (Trisomy 13) Turner syndrome (Monosomy X) Klinefelter syndrome (Extra X) 5:00 AM

Some important points to remember Nondisjunction is more likely to occur during oogenesis than during spermatogenesis. 5:00 AM

Some important points to remember Nondisjunction is more likely with increasing maternal age. No environmental agents (e.g., radiation, alcohol) have been shown to have measurable influence. 5:00 AM

Some important points to remember Nondisjunction is more likely in meiosis I than meiosis II. 5:00 AM

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