Human Cytogenetic

8/11/2019 Human Cytogenetic

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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 (-)

Human Cytogenetic

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