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Human Cytogenetic
By : E. Suryadi
School of MedicineGadjah Mada University
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The Past of Human Cytogenetics (HC)
Before 1956, the human chromosome number
was believed to be 48
The discovery of Tjio and Levan (1956) thatthe human chromosome number is 46, then
the starting point for subsequent spectacular
developments in human chromosome studies
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Hsu (1979) divides HC into foureras
A. the dark age, before 1953
B. the hypotonic period , from 1953-1958
C. the trisomy period, between 1959-1969
D. the chromosome banding era 1970- stillcontinue
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The Future of HC
Cytogenetic studies have in many casesreached the point at which molecular biologytakes over.
However, without the basic cytogeneticknowledge molecular genetic works would notbe possible.
Chromosome analyses have uncovered thecauses of many birth defect and abortions,infertile men,women with gonadal dysgenesismental retardates ect.
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Number, Structure & Karyotype
Human somatic cells contain 46 chromosome
organized into 22 autosome pairs plus sex
chromosome
The basic haploid set (n =23) is present in the
gamet (germ) cell
Size and shape of each chromosomes are
difference
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Chromosome analysis
During mitotic metaphase the condensed
chromosomes appear in identifiable
shapes characteristic of the karyotype of
the species being studied
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Chromatid
Metaphase chromosome consist of two sisterchromatids
Each chromatid contains ; one double helix of DNA continue from one end
of the chromosome to the other several different type of protein
Human Chromosome range in size from somewhat larger than 5 micron to less than 1micron
When DNA stretched out about 5 cm longevery chromatid
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Types protein in Human Chromosome
1. Histon protein contain five types:
(H1, H2A, H2B, H3,and H4)
Role of the histons : conservation in the higher
organism Nucleosom is smallest structure combining DNA and
histon
2. Non histon chromosomal protein:
Varies widely among different cell types of the same
organism
Role in the regulation of expression of specific genes
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Non-cromatinNuclear
constituent
DNA
histone
Non histone
protein
RNA
Komponen penyusun
strukture nucleus
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15 to 100 nucleotide
Pairs depend on cell
types
140 nucleotide
pairs
8 histone molecules
Chromatin stretched during
Preparation for electron microscopy,
Revealing spacers or linkers
between nucleosomes
Nucleosomes
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Shape of Human Chromosome
During metaphase stage the chromosomes
like X shape.
At crossing called centromere, and parts of
end chromosome are called telomere. Based on centromere position, kinds of shape
chromosome divided:
Metacentric o subtelocentric
Submetacentric o telocentric
Acrocentric o have satelites
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Parts of chromosome
Between centromere and telomere called
arm.
Two kinds of arm :
p = petite ; short arm
q : long arm
The arm ratio or centromere index is
sometimes sufficient to permit
identification of chromosome
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Prenatal studies
Taking a sample of amnionic fluid and
trophoblastic (chorion villi)
Important for prenatal diagnostic
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Principal of chromosome analysisprocedure
Cell culture
Metaphase stop
Cell hypotonic shock
Fixation
Cytologic preparation
Staining or banding
Photography
karyotyping
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Classification of Human Chromosome
Based on Human Chromosomeclassification
1. Large of chromosome
2. Shape of chromosome
two kinds classification
1.using number, from 1 to 22 and X & Y
2.using capital letter: A,B,C,D,E,F,G .
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Nomenclature of Human Chromosome
Based on Paris Conference (1971)
Telomeres, centromeres and number of
prominent band are used as landmarks
A section of a chromosome between two
landmarks is called a region, and these
regions are numbered 1, 2, 3 and so on
in both direction starting from the
centromere
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Nomenclature
Each of region divided band parts, thesebands are numbered 1, 2, , 3, 4, and so on.
Each of band divided sub-band, these sub-
band are numbered 01, 02, 03, and so on or.1, .2, .3, and so on
When the sub-band is further subdivided anadditional digit is added.
For example 14q32033. Or 14q32.33.
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p
q
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Idiogram
An idiogram is a diagrammatic karyotype
based on chromosome measurements in
many cells.
Morphological identification is based on
the relative sizes of the chromosomes
and their arm ratios
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i i f h l
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Description of term Chromosomalanalysis
EUPLOID/DIPLOID
Chromosome numbers are multiples of haploidset (2n)
POLYPLOIDChromosome numbers are greater than diploid
(3n, triploid)
ANEUPLOID
Chromosome numbers are not exact multiples ofthe haploid set (2n+1 trisomy; 2n-1monosomy)
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Description
MOSAIC
Presence of two different cell lines
derived from one zygote (46XX,45X,
Turner!s mosaic)
CHIMAERA
Presence of two different cell lines
derived from fusion of two zygotes
(46XX,46XY)
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Reporting of Karyotypes
Total number of chromosomes given first
followed by constitution of sex chromosomes
Additional or lost chromosomes are indicated
by + or Structural rearrangements are described
identifying p and q arms and location of
abnormality
46, XY, del 11 (p13) : male with deletion of
short arm of chromosome 11 at band 13
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I di ti f t ti
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Indication for cytogenetic
examination
Known or suspected a chromosomalabnormality
Multiple congenital anomalies, especially whenassociated with growth and mental retardation.
Sexual differentiation abnormality Familier mental retardation
Hematologic Malignancies or other neoplasia
Habitual abortion or multiple miscarriages
Neonatal death and unexplain birth death
Infertility
Cli i l f
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Clinical consequences of
chromosome abnormalities
Spontaneous abortions: trisomy(16),monosomy, triploidy, tetraploidy
- At least 7.5% of conceptions have majorchromosome abnormalities and theseconceptions almost aborted spontaneous
Birth defect about 1/170 : Down Syndrome,trisomy 18 (Edwards), trisomy 13 (Pataus),
5p-Syndrome ( cri-du-chat) Chromosomal changes in neoplasm: Burkitt
lymphoma, Chronic myelogenous leukemia
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Chromosome nomenclature
A-G chromosome groups
1-22 autosome numbers X,Y sex chromosomes
/ diagonal line indicates mosaicism
p short arm of chromosome
q long arm of chromosome
del deletion
der derivative o chromosome
dup duplication
i isochromosome
ins insertion
inv inversion
r ring chromosome t translocation
ter terminal
+ or indicate addition (+) or loss (-)
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