An Introduction to Cytogenetics

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an introduction to Cytogenetics

We are just in the beginning !

The Principles of Clinical Cytogenetics should be divided into sections:

FIRST An overview on the historical perspective Explanation of the concepts involved Description of cytogenetic nomenclature Examples of its use.


An overview of the processes involved to provide a fundamental understanding of the labor-intensive nature of chromosome analysis


the main focus SHOULD BE ON the various applications of chromosome analysis in clinical settings and the significance of abnormal results

Cytogenetics techniques are:

Confusing C Complex C Concise; Muck background and training C Capable; the role is increasing (a new era !) C

Morphology Histology Histopathology Cytology Special staining Using markers (FC, IHC) Cytogenetics Molecular Genetics

Histochemical staining

M-I-CMorphology Immunophenotyping Cytogenetics


Cytogenetic and Molecular genetic


Micro gene array the idea is existing since mid-80s

Modern Diagnostics in Cancer Management: A multi-modal Approach




Articles in the Medline database with reference to flow cytometry




1974: first article



01970 1972

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998


Increasing reference to (Flow Cytometry) in the medical literature over the past 3 decades(Alice Longobardi Givan. Flow Cytometry First principles, 2nd edition. Preface article, 2001, A John Wiley & Sons Inc., Publication)

The first impedance based flow cytometry to count cells using 1953 the coulter principle (by Wallace A Coulter, USA). The first fluorescence-based flow cytometer was developed (Wolfgang Ghde, University of Munster, Germany).


Remarkable change on the size of the flow cytometer and 2000s software capability, and up to 17 color could be used at a time.

Just in the last decade the great discoveries of the cell, the nucleus, the chromosome, and DNA have been initiated An emphasis placed by some on determining the correct number of chromosomes in humans. 1912, von Winiwarter concluded that men have 47 chromosomes and women have 48 !!! 1923, Painter studied (meiotic) chromosomes derived from the testicles Texas State Insane Asylum He definitively reported the human diploid chromosome number to be 48 (double the 24 bivalents he saw) Two years earlier, he had preliminarily reported that some of his better samples produced a diploid number of 46. He also proposed the X and Y sex chromosome mechanism in man. One year later, Levitsky formulated the term karyotype to refer to the ordered arrangement of chromosomes.

The references for the previous 2 works: Painter, T.S. (1923) Studies in mammalian spermatogenesis. II. The spermatogenesis of man. J. Exp. Zool. 37, 291-336

Levitsky G.A. (1924) Materielle Grundlagen der Vererbung. Staatsverlag, Kiew

Jrme Lejeune receives a Joseph P. Kennedy, Jr. Foundation International Award Down syndrome results from an extra chromosome December, 1962

The study of human chromosomes plays a role in 1) Diagnosis 2) Prognosis 3) Monitoring of treatmentThe involving conditions seen not only by medical geneticists and genetic counselors, but also by: a) Pediatricians b) obstetrician/gynecologists c) Perinatologists d) Hematologists e) Oncologists f) Endocrinologists g) Pathologists h) Urologists i) Internists j) Family practice physicians.

Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes: 1) Routine analysis of G-Banded chromosomes 2) Other cytogenetic banding techniques 3) Molecular cytogenetics such (FISH and CGH)

Since its first application to the study of cancer, cytogenetics has taken us:FROM a state of virtually no knowledge of the chromosome changes in human cancer TO a point at which a staggering body of information is available The latter is evidenced by the nearly 55,000 Cancer karyotypes now included in: (Mitelman Database of Chromosome Aberrations in Cancer)

American College of Medical Genetics

International Standing Committee on Human Cytogenetic Nomenclature ISCN

Cytogenetic testing is often an issue for hospital laboratory personnel and managed care organizations, yet cytogenetics is often less well understood than most specialized laboratory testing.


Cytogenetic testing is often an issue for hospital laboratory personnel and managed care organizations, yet cytogenetics is often less well understood than most specialized laboratory testing.


Cytogenetic testing is often an issue for hospital laboratory personnel and managed care organizations, yet cytogenetics is often less well understood than most specialized laboratory testing.

Why?One can attribute this to several causes: The cytogenetics lab is essentially the only setting in which living cells are required for traditional testing. This unusual sample requirement is a potential source of confusion. Cytogenetics is still perceived, and rightly so, to be as much art as it is science in an era when most clinical testing is becoming more and more automated or high tech. Genetics in general still does not receive sufficient emphasis in the training of medical personnel.

Karl Wilhelm von Ngeli 27th March, 1817-11th May, 1891 a Swiss botanist, studied cell division and pollination

Walther Flemming

1843 - 1905 German biologist and a founder of cytogenetics. He became the director of the Anatomical Institute and stayed there until his death.

The hand drawing of Flemming: Illustrations of cells with chromosomes and mitosis From the book Zellsubstanz, Kern und Zelltheilung

Drawing of a salivary gland cell as published by Flemming. One of over 100 drawings from Flemming's book Zellsubstanz, Kern und Zelltheilung 1885

He was first that:Studied cell division and chromosomes in details and Published the results in his book (1881-2)

A great step forward in cell biology, occurred? The process of cell division studied in great detail, With the help of powerful new microscopes and dye staining techniques.

Carnegie Institute for scienceWashington DC, USAA joined project between:


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13 13


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(explore the world under the microscopic)

1312 10 13 13 13

Earth Science

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The great discoveries in Biology -13-

1) Microorganisms (1674( Microscope lens grinder Anton Van Leeuwenhoek accidentally discovers microorganisms in a drop of water. Using his own microscopes, he observes sperm, bacteria and red blood cells. His observations lay the foundation for the sciences of bacteriology and microbiology.

The great discoveries in Biology -132) The Cell Nucleus (1831) While studying an orchid family, botanist Robert Brown identifies the detailed structure within the cells and recognized the nucleus inside the cell.

orchid family is a diverse and widespread family of flowering plants with colorful and fragrant blooms .

The great discoveries in Biology -133) Archaea (1977) Carl Woese an American microbiologist and physicist, famous for defining the Archaea (a new kingdom of life) in 1977. He discovers bacteria are not the only simple-celled prokaryotes on Earth. His three-domain system, based on genetic relationships rather than obvious morphologic similarities, divided life into 23 main divisions, incorporated within three domains: Bacteria, Archaea, and Eucarya.

The great discoveries in Biology -134) Cell Division (1879) Walther Flemming carefully observes that animal cells divide in stages mitosis Eduard Strasburger independently identifies a similar process of cellular division 5) Sex Cells (1884) August Weismann identifies that sex cells must have divided differently to end up with only half of a chromosomal set. This very special division of sex cells is called meiosis. 6) Cell Differentiation (late 19th century( Several scientists participate in the discovery of cell differentiation, eventually leading to the isolation of human embryonic stem cells. During differentiation, a cell turns into one of the many cell types. Cells that are not yet differentiated and have the potential to become any type of cell are called stem cells.

The great discoveries in Genetics -131) Rules of Heredity (1850s(Gregor Mendel (Austrian monk and botanist) discovers how genetic information is passed down through generations. Mendel's findings are ridiculed during his lifetime and he dies never knowing that he would come to be known as the "father of genetics".

2) Genes Are Located on Chromosomes (1910 1920s)Thomas Hunt Morgan discovers that genes are located on chromosomes.

3) Genes Control Biochemical Events (1930(George Beadle and Edward Tatum discover that genes are responsible for the production of enzymes. Their report is the genesis of the "one gene-one enzyme" concept.

The great discoveries in Genetics -13-

4) Some Genes Can Jump (1940(Barbara McClintock discovers transposons (genes that can jump on a chromosome) while seeking to explain color variations in corn. Transposons are segments of DNA that can mov