1. Cytogenetics Part 1 Dr. Mohammed Hussein
M.B.Ch.B, MSC, PhD, DCH (UK), MRCPCH
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2. Numerical Chromosomal Abnormalities
Introduction
Numerical Chromosomal Abnormalities
Structural Chromosomal Abnormalities
Advances in Molecular Cytogenetics
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3. Introduction
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4. 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
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5. Karyotyping
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6. 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
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9. Karyogram Karyogram represents a drawing of each type of chromosome
The presentation is haploid (only one copy of each chromosome is shown)
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11. 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
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12. NOT X q twenty-two point one2 2 .1
X q two-two point one
NOT X q twenty-two point one
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13. Chromosome Nomenclature
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14. 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
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15. 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
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16. 21, 22, 13 , 14 , 15 Mnemonic Acrocentric chromosomes 1,2,3,4,5
21, 22, 13 , 14 , 15
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17. 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
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19. 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)
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20. Chromosome Abnormalities
Numerical Chromosomal Abnormalities
Structural Chromosomal Abnormalities
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21. 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)
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22. Triploidy
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23. 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
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24. Tetraploidy
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25. Tetraploidy
This lethal condition is much rarer than triploidy among live births
Only a few cases have been described
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26. Aneuploidy
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27. 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) (+)
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28. Aneuploidy Autosomal aneuploidy Sex chromosome aneuploidy Monosomy (–)
Trisomy (+)
Sex chromosome aneuploidy
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29. Autosomal aneuploidy
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30. 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
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31. Trisomy 13 (Patau Syndrome)47
,XX
,+13
47,XY,+13 or 47,XX,+13
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33. Trisomy 18 (Edward Syndrome)47
,XY
,+18
47,XY,+18 or 47,XX,+18
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35. Trisomy 21 (Down Syndrome)47
,XX
,+21
47,XY,+21 or 47,XX,+21
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39. Sex chromosome aneuploidy
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40. Sex chromosome aneuploidy
Relatively common
Have less severe consequences than does autosomal aneuploidy.
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41. 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)
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42. 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
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43. 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
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44. Klinefelter Syndrome 47
,XXY
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47. Turner Syndrome 45 ,X or
45,XO
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49. Linda Hunt
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50. Triple X Syndrome 47
,XXX
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52. 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
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53. Nondisjunction is the usual cause of aneuploidies
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54. Disjunction during Meiosis I Disjunction during Meiosis II
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55. Non-disjunction during
Meiosis I
Disjunction during
Meiosis II
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56. Non-disjunction during
Meiosis I
Non-disjunction during
Meiosis II
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57. 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)
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58. Some important points to remember
Nondisjunction is more likely to occur during oogenesis than during spermatogenesis.
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59. 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.
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60. Some important points to remember
Nondisjunction is more likely in meiosis I than meiosis II.
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