OVERVIEW

Clinical cytogenetics is the evaluation of chromosomes, their structure and inheritance, as applied to the practice of medical genetics. Chromosome analysis is an important diagnostic tool in numerous areas of clinical medicine for both constitutional and neoplastic disorders, although it should be noted that Medicare does not expect to see use for constitutional disorders nearly in the same proportion as it does for use for neoplastic diseases. Conventional cytogenetic analysis, for routine clinical purposes, using either non-neoplastic tissue (constitutional cytogenetics) or neoplastic tissue (cancer cytogenetics), includes:

1. Tissue culture of the specimen.
2. Metaphase arrest of dividing cells with chemicals that inhibit the mitotic spindle.
3. Exposure to hypotonic solution to swell the cells and thus release the chromosomes.
4. Slide preparation and staining, which permits the microscopic analysis of each chromosome in a metaphase preparation, to enable the observation of any aberrations.
5. Preparation of images called karyotypes, either on paper or electronically, which display all the chromosomes of a metaphase.
6. Interpretation of the results (normal or abnormal) within the context of the patient's indication for the study and clinical presentation.
7. Generation of a report, which conveys the patient results in cytogenetic nomenclature.

A uniform system of chromosome identification is internationally accepted for the identification of human chromosomes and the designation of abnormalities that are present. Such chromosomal analysis can detect various types of aberrations that fall into two major groups: Numerical (gain or loss of whole chromosomes) and structural (alteration of the structure of one or more chromosomes).

FACULTY:

Carlos Tirado, Ph.D. (Cytogenetics Laboratory Director)

Prasad Koduru, Ph.D.

DURATION: 1 month

PREREQUISITES:

None.

OBJECTIVES

Patient Care

Medical Knowledge

Practice based learning

Interpersonal and Communication Skills

Professionalism

Systems-based practice

CONFERENCES

BASIC READING

Week One: Constitutional Disorders (Didactic)

Required Reading

Nussbaum RL, McInnes RR, Willard HF. Thompson and Thompson Genetics in Medicine, 6th ed. Philadelphia: W.B. Saunders Co., 2001.
Chapters 1 (Introduction), 2 (Chromosomal Basis of Heredity), 3 (The Human Genome: Structure and Function of Genes and Chromosomes). 9 (Principles of Clinical Cytogenetics), and 10 (Clinical Cytogenetics: Disorders of the Autosomes and the Sex Chromosomes).

Cotran RS, Kumar V, Robbins SC. Robbins Pathologic Basis of Disease, 7th ed.  Philadelphia: W.B. Saunders Co; Chapters 5 and 10

Week Two:  Myeloid Disorders/Lymphoid Disorders (Didactic)

Myeloid Disorders

Jaffe ES, Harris NL, Stein H, Vardiman JW. WHO:  Pathology and Genetics-Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, 2001.

WHO: Tumors of Haematopoietic and Lymphoid Tissues
http://www.infobiogen.fr/services/chromcancer/Anomalies/Anomliste.html

Week Three:  Fluorescence in situ hybridization (Didactic)

Fluorescence In Situ Hybridization American College of Medical Genetics Prenatal Interphase Fluorescence In Situ Hybridization (FISH) Policy Statement . . .
http://www.faseb.org/genetics/acmg/pol-14.htm

FISH  (Fluorescence In Situ Hybridization) National Human Genome Research Institute,
http://www.accessexcellence.org/AB/GG/fish.html

Mountain States Genetics Network,
http://www.mostgene.org/gd/gdvol13a.htm

Week Four:  Solid Tumors (Didactic)

Fletcher CDM, Unni KK, Mertens F.  WHO: Pathology and Genetics-Tumours of Soft Tissue and Bone. IARC Press, Lyon, 2001.

WHO Pathology & Genetics:  Tumours of Soft Tissue and Bone
http://www.infobiogen.fr/services/chromcancer/Tumors/Tumorliste.html

ADDITIONAL READING AND SOURCES

(All books and atlases available in directors' offices)

Historical Perspective:

Hsu TC.  Human and Mammalian Cytogenetics, New York:  Springer-Verlag, 1979.

Human Cytogenetics:

Barch, M.J., Knutsen T. and Spurbeck, J.L. (eds.) (1997)   The AGT Cytogenetics Laboratory Manual, 3rd ed.  New York:  Raven Press.

Therman E, Susman M.  Chapter 1:  Origins and directions of human cytogenetics.  In: Human Chromosomes.  Structure, Behavior and Effects, 3rd ed.  New York:  Springer-Verlag, 1993.

Mitelman F:  Catalogue of Chromosome Aberrations in Cancer, 5th edition (2 volumes), New York:  Wiley-Liss, Inc., 1994.

Clinical Atlases:

Jones KL:  Smith's Recognizable Patterns of Human Malformation, 5th edition, Philadelphia:  W.B. Saunders Co., 1997.

Schinzel A:  Catalogue of Unbalanced Chromosome Aberrations in Man, Berlin, Germany,:  Walter de Gruyter, 2001.

Human Genetics Texts:

Scriver, Beaudet AL, Sly WS, Valle D (Eds.)  The Metabolic and Molecular Bases of Inherited Disease, 8th edition, New York, New York:  McGraw-Hill, 2001.

Rimoin DL, Connor JM, Pyeritz RE, Korf BR:  Emery and Rimoins Principles and Practice of Medical Genetics, 4th edition,  London: Harcourt Publishers Limited, 2002.

Prenatal Diagnosis and Genetic Counseling:

Gardner RJM, Sutherland GR:  Chromosome Abnormalities and Genetic Counseling, 2nd edition, New York:  Oxford University Press, 1996.

Journals Featuring Human Cytogenetics

American Journal of Human Genetics	Human Molecular Genetics
American Journal of Medical Genetics	Journal of Heredity
Annals of Human Genetics	Journal of Medical Genetics
Blood	Leukemia
British Journal of Haematology	Leukemia & Lymphoma
Cancer Genetics & Cytogenetics	Nature Genetics
Cytogenetic and Genome Research	Prenatal Diagnosis
Chromosoma	Somatic Cell Genetics
Genes, Chromosomes & Cancer	Hereditas
Genomics	Human Genetics
Human Heredity