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In humans, the normal diploid number of chromosomes is 46, consisting of 22 pairs of autosomal chromosomes (numbered 1–22 in decreasing size) and one pair of sex chromosomes (XX in females and XY in males). The genome is estimated to contain approximately 25,000 genes. Even the smallest autosome contains between 200 and 300 genes. Not surprisingly, duplications or deletions of chromosomes, or even small chromosome segments, have profound consequences on normal gene expression, leading to severe developmental and physiologic abnormalities.

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Deviations in number or structure of the 46 human chromosomes are astonishingly common, despite severe deleterious consequences. Chromosomal disorders occur in an estimated 10–25% of all pregnancies. They are the leading cause of fetal loss and, among pregnancies surviving to term, the leading known cause of birth defects and mental retardation.

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In recent years, the practice of cytogenetics has shifted from conventional cytogenetic methodology to a union of cytogenetic and molecular techniques. Formerly the province of research laboratories, fluorescence in situ hybridization (FISH), genomic array analysis, and related molecular cytogenetic technologies have been incorporated into everyday practice in clinical laboratories. As a result, there is an increased appreciation of the importance of "subtle" constitutional cytogenetic abnormalities such as micro-deletions and imprinting disorders, as well as previously recognized translocations and disorders of chromosome number.

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Conventional Cytogenetic Analysis

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In theory, chromosome preparations can be obtained from any actively dividing tissue by causing the cells to arrest in metaphase, the stage of the cell cycle when chromosomes are maximally condensed. In practice, only a small number of tissues are used for routine chromosome analysis: amniocytes or chorionic villi for prenatal testing and blood, bone marrow, or skin fibroblasts for postnatal studies. Samples of blood, bone marrow, and chorionic villi can be processed using short-term culture techniques that yield results in 1–3 days. Analysis of other tissue types typically involves long-term cell culture, requiring 1–3 weeks of processing before cytogenetic analysis is possible.

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Cells are isolated at metaphase or prometaphase and treated chemically or enzymatically to reveal chromosome "bands" (Fig. 62-1). Analysis of the number of chromosomes in the cell and the distribution of bands on individual chromosomes allow the identification of numerical or structural abnormalities. This strategy is useful for characterizing the normal chromosome complement and determining the incidence and types of major chromosome abnormalities.

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Figure 62-1
Graphic Jump Location

A. An idealized human chromosome, showing the centromere (cen), long (q) and short (p) arms, and telomeres (tel). B. A G-banded human karyotype from a normal (46,XX) female.

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Each human chromosome contains two specialized structures: a centromere and two telomeres. The centromere, or primary constriction, divides the chromosome into short (p) and long (q) arms and is responsible for the segregation of chromosomes during cell division. The telomeres, or chromosome ends, "cap" the p and ...

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