Chromosomes are cellular structures that carry genes. They are composed of DNA and protein and are found in the nucleus of cells. Genetic information is contained in the linear sequence of DNA bases on chromosomes. There are normally 46 chromosomes in humans arranged into 22 paired autosomes and two sex chromosomes. Chromosomal abnormalities can be numerical, involving extra or missing chromosomes, or structural, involving changes in chromosome structure like deletions, translocations, or inversions. Karyotyping allows visualization of chromosomes and identification of any abnormalities.

1. Rabab Salama
Clinical and Chemical Pathology Consultant
HCQM Specialist
Karyotyping

2. What Are Chromosomes?
Chromosomesare the cellular
structures
that carry genes
OR
Chromosomes are distinct dense bodies found
in the nucleus of cells , composed of protein
and DNA.

4.  The DNA in an individual chromosome is
one, long molecule which is highly
coiled and condensed.
 Genetic information is contained in the
DNA of chromosomes in the form of
linear sequences of bases (A:adenine,T:
thymine,C:cytosine,G:guanine).
What Are Chromosomes?

6. DNA ( Deoxyribonucleic acid)
&RNA (Ribonucleic acid)
 In DNA the sugar is deoxyribose and the bases are
Adenine (A), Cytocine (C), Guanine (G) and Thymine
(T).
 Nucleotides are linked to one another by
phosphodiester bonds to form DNA polymer or
polynucleotide.

7. DNA ( Deoxyribonucleic acid)
&RNA (Ribonucleic acid)
 DNA is a double stranded, two polynucleotide being
wound around one another to form double helix.
 The double helix is held together by hydrogen bonds
between the base components of the nucleotide s of
the two strands.

8. The base pairing rules that:
1. A base-pairs with T.
2. G base- pairs with C
DNA ( Deoxyribonucleic acid)
&RNA (Ribonucleic acid)

9. DNA ( Deoxyribonucleic acid)
&RNA (Ribonucleic acid)
 So the two DNA molecules in the double
helix have complementary sequences.
 In the RNA the sugar is ribose and the
thymine base is replaced by the uracil
(U).
 RNA is usually single stranded.

10. The total number
of bases
 In all the chromosomes of a
human cell is approximately six
billion
 In an individual chromosome
range from 50 to 250 million
base.
What Are Chromosomes? (Cont)

11. Gene:
 The DNA sequence for a
single trait.
What Are Chromosomes? (Cont)

12. Gene:
 Each chromosome contains a few
thousand genes.
 The estimate for the number of genes in
humans are thought to be between
30,000 and 40,000 genes.
What Are Chromosomes? (Cont)

13. Gene:
 Genes can be as short as 1000 base pairs or
as long as several hundred thousand base
pairs. It can even be carried by more than one
chromosome
 The smallest band detected by light
microscope is about 5-10 million base pair and
could harbor 10-50 genes.
What Are Chromosomes? (Cont)

14. From Gene to Protein

15. From Gene to Protein

17. 46
Chromosomes
22 autosomal
pairs
2 sex
chromosomes
Normal Karyotype
46,XY46,XX F
M

18. General Guidelines:
 Modal number, sex chrom, abn abbrev (first
chrom; second chrom) (arm band number; arm
band number)
Ex:
 46,XX,t(1;2)(p32;q22)
 Modal number: total count of number of
chromosomes in each cell of a given cell line

19. How to Visualize
Chromosomes ?

20. Cytogenetic Techniques
 Conventional (standard) banding techniques (G
banding most commonly used).
 Chromosomal abnormalities that cannot be
resolved by G banding may be discovered by:
 Molecular cytogenetic techniques (Fluorescence
in Situ Hybridization FISH ).

24. Conventional Cytogenetic Analysis
Culture
Hypotonic
Fixation
Slide
preparation
Staining

27. Metaphase Spread
Under the microscopeChromoscan

28. Cytogenetic Nomenclature
 Each chromosome is visualized
as two chromatids that are
joined at a central
constriction called the
centromere.
 The centromere divides the
chromosomes into two arms: a
short arm (P) and a long
arm (q)
 Telomere

29. Position of Centromere

30. Identifying Features of a
Chromosome
 Size (large, medium, small)
 Position of centromere
metacentric acrocentric
submetacentric
 Banding pattern

31. Banding Techniques
 Chromosomes appear as a
continuous series of light
and dark areas, called
bands depending on their
nucleotide and protein
composition.

32.  Each chromosome (1,2,3...22,
X and Y) displays a unique
banding pattern, analogous to
a "bar code", which allows it
to be reliably differentiated
from other chromosomes of
the same size and centromeric
position.
Banding Techniques

33. Chromosome Band
 Part of a chromosome
that is distinguished
from adjacent parts by
appearing darker or
lighter with one or more
banding techniques.

34.  Each chromosome has landmarks
which is used to designate
morophologic features
important to identify the
chromosomes:
 Centromere
 Telomere
 Prominent bands
Telomere
Telomere
Centromere

35. Chromosome Region
 Area lying between
adjacent landmarks.
 Ranges 1-4.
 Numbered sequentially
from centromere to
telomere.

36.  Regions are divided into
bands, numbered
sequentially from
centromere to telomere
(1q31).(21q22).(19p13)
 In high resolution banding,
bands are divided into sub-
bands. (1q31.1).
Chromosome Region

37. A Karyotype
 Arrangement of chromosomes from a
particular cell, the largest chromosomes
are first and the smallest ones are last.
 It is a description of the number and
structure of the chromosomes.

38. Chromosomes are divided into 7 groups,
A………G
 Group A: 1,2,3
 Group B: 4,5
 Group C: 6-12, x
 Group D: 13,14,15
 Group E: 16,17,18
 Group F: 19,20
 Group G: 21,22,Y

39. Chromosomal Abnormalities
 Numerical:A karyotype with
abnormal No. of chromosomes.
 Structural:Alterations in the
structure of chromosomes.

40. Hyperdiploid: more than 46 chromosomes.
Low Hyperdiploidy (47-50) Childhood ALL
High Hyperdiploidy (51-60) Childhood ALL
Near Tetraploidy
Near Triploidy
Numerical Abnormalities

41. • Trisomy: gain of one copy (47,xy,+8)
The obvious molecular consequence of a trisomy is
the presence of an additional copy of all of the
genetic material on a chromosome.
• Tetrasomy: gain of two copies
Numerical Abnormalities

42. Hypodiploid: Less than 46
chromosomes.
• Monosomy: loss of one copy (45,xy,-7).
• Nullisomy: loss of both copies.
Numerical Abnormalities

45. High Hyperdiploidy
(55,xy,+3,+7+7+14+14+17+20+21+21)

47. Trisomy 8 (47,xy,+8)

49. Hypodiploidy
(37,XX,-2,-3,-8,-10,-12,-13,-15,-19,-22)

51. Monosomy 7 (45,xx,-7)

52. Deletion (del) = loss of chromosomes
segments.
 Interstitial
 Terminal
Structural Abnormalities

54. 46,xy,del (5)(q31)

57. 46,xy,del(7)(q22;q32)

58. Translocation
Translocation (t): relocation of material
from one chromosome to a different
chromosome.
 Reciprocal: exchange of material
between different chromosomes.
t(9;22)(q34;q11)
 Non-reciprocal: rare

59. Reciprocal Translocation

60. Translocation

62. 46,xx,t(9;22)(q34;q11)

64. 46,xy,t(8;21)(q22;q22)

65. Translocations: chch features of hematologic
malignancies two mechanisms
1- Generation of fusion protein
 PML-RARA in t(15;17) in M3
(inhibit apoptosis, differentiation block)
 BCR-ABL in t(9;22) in CML
(Increased proliferation, inhibit apoptosis, increase
cell adhesive abnormalities)

66. Inversion
Inversion (inv): it is 180o rotation of a
chromosome segment
 Pericentric
 Paracentric

67. Inversion

69. 46,xy,inv(16)(p13;q22)

70. Isochromosome
 Isochromosome (i): Two identical chromosome
arms positioned as mirror images of each other
[i(17q)]
 Isochromosome formation leads to both loss and
gain of genetic material
 i(17q) consists of two chromosome 17 long arms,
without short arms. Cells with i(17q) generally also
have one normal chromosome 17; thus, they have one
copy of 17p and three copies of 17q.

71. Isochromosome

72.  Diploid cell: A cell with a normal
complement of structurally normal
chromosomes.
 Pseudodiploid cell: A cell with 46
chromosomes but with numerical
chromosomal abnormality (e.g. loss of
one chromosome & gain of another) or
structural abnormality.
 Aneuploid cell: Cell with abnormal
number of chromosomes.