Chromosomes

Chromatin and DNA synthesis

- The chromatin is formed of repeating units of

DNA.

- DNA, helically, is formed of the longest naturally

existing macromolecules which are present in the
from of polymers.

Chromosomes

 Chromosomes are no more than the chromatin granules seen in the nuclei of the cells
during the interphase stage of the cell cycle; they are double helical DNA thread with
different coiling tendencies. The repeated units of chromatin granules called
nucleosomes.
 They are named for their ability to take up certain stains

Morphology:

 The chromosome appears as a cross-shaped structure due to the union of its 2

chromatids(S-chromosomes) at the central region known as the centromere.
 It has 4 arms radiating from the point of the centromere

(long arm —q and short arm — p ).

 The stainability of the chromosome is

not homogenous along the whole
length of its75 chromatids.

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Classification:

A) According to the position of centromere:

The chromosome may be:

 metacentric — the centromere is of median position and the 4

arms are equal in length.
 Submetacentric — the centromere is of a submedian position with
2 short and long arms.
 Acrocentric — the centromere is of a subterminal position with 2
exceeding short arms and 2 long arms.
 telocentric — the centromere is of a terminal position with only
apparently long arms.

B) Denver classification:

The chromosome set can be classified into 7 groups (A-G) in according to the chromosome
engin. the position of the centromere and the presence of specific landmarks.

 Group A:
 chromosome 1,2 and 3.
 Large with approximately median centromeres. ‘
 2 is my submetacentric.
 Group b:
 chromosome 4 and 5.
 Large with submetacentric centromeres.
 Group C:
 chromosome 6-12 and X.
 median-sized submetacentric.
 Group D:
 Chromosome 13, 14 and 15.
 Median-sized acrocentric.
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 Group E:
 Chromosome 16, 17 and 18.
 Short submetacentric.
 16 nearly metacentric.
 Group F:
 Chromosome 19 and 20.
 Short metacentric.
 Group G:
 chromosome 21, 22 and Y.
 very short acrocentric.
 Y is the largest one and tend to be at the periphery of the karyotype.

NE:

This array of chromosomes in a form suitable for analysis is called a karyotype. A diagrammatic

representation of the karyotype is an ideogram.

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Identification of chromosomes:

1. Morphological approach:

 Arms_ long or short

 centromeric index
 morphological features

2. Autoradiography:

 Permits the localization of radioactive substamces in tissue by means of the effect of

emitted radiation on photographic emulsion.
 The base thymine is the ideal marker for DNA synthesis because it is present only in
DNA.
 The new strand of DNA molecule is labeled only because the old strand of DNA molecule
is devoid of any radioactive label.

3. Chromosomal banding:

 It is a part of chromosome that is clearly distinguishable from its adjacent segments by

appearing darker or lighter as a result of new staining

Types of banding:

A. Quinacrine-bands (Q-bands)
B. Giemsa-bands (G-bands)
C. Reverse-bands (R-bands)
D. Constitutive heterochromatin bands(C-bands)
E. High resolution banding

4- Fluorescence in situ hybridization (FISH)

Clearly identifies the chromosomes in both metaphase and interphase

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Chromosomal anomalies (aberration)

A)Numerical :

It result from disturbances’ of chromosomes movement and/ = or distribution during cell

division. These lead to changes in chromosomes number and may involve individual
chromosomes or whole chromosomes complements.

Types:

A) Aneuploidy: is an abnormality of the number of single chromosomes in which pair of

homologous chromosomes will be missing one member (monosomy) or having an extra-
member (triosomy). In some cases, the 2 members of a pair missed’ and the cell is described
to be nullisomic.

 Triosomy 21— Down syndrome Triesomy X — Klinefelter syndrome (47, XXY)

Monosomy X — Turner syndrome (45, XO)

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B) Euploidy: is a defect of a genome level; affecting the total haploid set (N)

 Haploidy: is described for the cell containing a single chromosome of all the
chromosome member.
 lriploidy: is a term applied when the cell contains 3 chromosomes of each member.

Similarly, tetraploidy, pentaploidy, polyploidy.

Causes:

1. Non disjunction.
2. Anaphase lagging
3. spindle apparatus defects
4. Drugs
5. viruses
6. Double fertilization

Mosaicism:

 A mosaic is an individual with 2 or more cell lines whish were derived from a single zygote.
 It results from either non disjunction or anaphase lagging.
 Many different mosaics have been reported e.g. 46/47, XO/XX, .....

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B) Structural:

It results from Chromosome breakage with or without subsequent union.

Types:

Deletion:

 It is a loss of any part of a Chromosome.

 If the breakage is single, it is called terminal.
 If there is are 2 breaks, it is called interstitial.
 If the deleted part lacks a centromere (acrocentric) , it will be lost in
the next division

Wolf syndrome is a partial loss of short arm chromosome 4 7

Ring chromosome:

 It is a special type of deletion that occurs when there are 2 breaks

at the 2 distal ends of the same chromosome and the broken ends
unite to form a ring.

Inversion:

 It results from 2 breaks occurring in a chromosome and the healing

of the fragments in such a way that a portion of the gene sequence of the chromosome
has become rearranged in a reverse order or with deletion of the break part.

Types:

A. Paracentric inversion
B. Pericentric inversion

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Translocation:

It is the transfere of chromosomal material between 2 chromosomes. The process requires

breakage of both chromosomes.

Types:

a) Reciprocal translocation:

 in which the chromosomal material distal to breaks in 2 chromosomes is exchanged as

in philadelphia chromosome (ch 9 and 22)

b) Robertsonian translocation:

 It arise from breaks at or near the entromere in 2 acrocentric non-homologous

chromosomes with cross-fusion of the products
 In most cases the breaks are just above the centromere and
so the products are a single chromosome with 2
centromeres (dicentric) and a fragment with no centromere
(acentric).
 Chromosomes14 and 21 are the most frequently involved.

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Insertion

 Insertion occurs when a segment of one chromosome inserted into another chromosome.

Isochromosome:

 It is an abnormal chromosome which has deletion of one arm with duplication of the
other (duplication deficiency)

Fragile chromosome

 The name comes from an unusual narrow place on the X chromosome that can be seen
in a microscope; it is called a fragile site.
 Fragile chromosome is
susceptible to chromosome
breakage.
 After Down syndrome, the
second most frequent genetic
cause of mental retardation is
fragile X chromosome.

Causes of structural anomalies:

A) lonizing radiation: it depends on dose, type of radiation and the period of exposure

B) Chemicals: as cytotoxic drugs, some antibiotics (tetracycline)

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