Human Cytogenetic

By : E. Suryadi
School of Medicine Gadjah Mada University

The Past of Human Cytogenetics (HC)
Before 1956, the human chromosome number
was believed to be 48

The discovery of Tjio and Levan (1956) that
the human chromosome number is 46, then
the starting point for subsequent spectacular
developments in human chromosome studies
Hsu (1979) divides HC into four
eras
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- still
continue
The Future of HC
Cytogenetic studies have in many cases
reached the point at which molecular biology
takes over.

However, without the basic cytogenetic
knowledge molecular genetic works would not
be possible.

Chromosome analyses have uncovered the
causes of many birth defect and abortions,
infertile men,women with gonadal dysgenesis
mental retardates ect.
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
Chromosome analysis
During mitotic metaphase the condensed
chromosomes appear in identifiable
shapes characteristic of the karyotype of
the species being studied
Chromatid
Metaphase chromosome consist of two sister
chromatids

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 some
what larger than 5 micron to less than 1
micron

When DNA stretched out about 5 cm long
every chromatid
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
Non-cromatin
Nuclear
constituent
DNA
histone
Non histone
protein
RNA
Komponen penyusun
strukture nucleus
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
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

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
Methods in HC
SAMPLING
1 Direct methods
Was done mostly on testicular tissue,
bone marrow biopsies.
Primitive techniques the human cytologist
2. Culture method tissue or Cell
At present, culture lymphocytes and
fibroblasts are the main sources of cell for
HC studies
Prenatal studies
Taking a sample of amnionic fluid and
trophoblastic (chorion villi)
Important for prenatal diagnostic
Principal of chromosome analysis
procedure
Cell culture
Metaphase stop
Cell hypotonic shock
Fixation
Cytologic preparation
Staining or banding
Photography
karyotyping

Classification of Human Chromosome
Based on Human Chromosome
classification
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 .
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
Nomenclature
Each of region divided band parts, these
bands 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 an
additional digit is added.
For example 14q32033. Or 14q32.33.






























































p
q
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

















































































































































































































































































































































Description of term Chromosomal
analysis
EUPLOID/DIPLOID
Chromosome numbers are multiples of haploid
set (2n)
POLYPLOID
Chromosome numbers are greater than diploid
(3n, triploid)
ANEUPLOID
Chromosome numbers are not exact multiples of
the haploid set (2n+1 trisomy; 2n-1
monosomy)
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)
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
Indication for cytogenetic
examination
Known or suspected a chromosomal
abnormality
Multiple congenital anomalies, especially when
associated 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
Clinical consequences of
chromosome abnormalities
Spontaneous abortions: trisomy(16),
monosomy, triploidy, tetraploidy
- At least 7.5% of conceptions have major
chromosome abnormalities and these
conceptions 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
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 (-)