Fig. 7.13 ). Thus, 2q34 indicates chromosome 2, long arm, region 3, band 4. The patterns of chromosomal rearrangement after breakage (
Fig. 7.14 ) are as follows: • Translocation implies transfer of a part of one chromosome to another chromosome. The process is usually reciprocal (i.e., fragments are exchanged between two chromosomes). In genetic shorthand, translocations are indicated by t followed by the involved chromosomes in numeric order—for example, 46,XX,t(2;5)(q31;p14). This notation would indicate a reciprocal translocation involving the long arm (q) of chromosome 2 at region 3, band 1, and the short arm of chromosome 5, region 1, band 4. When the entire broken fragments are exchanged, the resulting balanced reciprocal translocation (
Fig. 7.14 ) is not harmful to the carrier, who has the normal number of chromosomes and the full complement of genetic material. However, during gametogenesis, abnormal (unbalanced) gametes are formed, resulting in abnormal zygotes. A special pattern of translocation involving two acrocentric chromosomes is called centric fusion type, or robertsonian, translocation. The breaks typically occur close to the centromere, affecting the short arms of both chromosomes. Transfer of the segments leads to one very large chromosome and one extremely small one (
Fig. 7.14 ). The short fragments are lost, and the carrier has 45 chromosomes. Because the short arms of all acrocentric chromosomes carry highly redundant genes (e.g., ribosomal RNA genes), such loss is compatible with survival. However, difficulties arise during gametogenesis, resulting in the formation of unbalanced gametes that could lead to abnormal offspring.
• Isochromosomes result when the centromere divides horizontally rather than vertically. One of the two arms of the chromosome is then lost, and the remaining arm is duplicated, resulting in a chromosome with only two short arms or two long arms. The most common isochromosome present in live births involves the long arm of the X chromosome and is designated i(Xq). When fertilization occurs by a gamete that contains a normal X chromosome, the result is monosomy for genes on Xp and trisomy for genes on Xq.
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Fig. 7.14 Typesofchromosomalrearrangements.
Deletion involves loss of a portion of a chromosome. A single break may delete a terminal segment. Two interstitial breaks, with reunion of the proximal and distal segments, may result in loss of an internal segment. The isolated fragment, which lacks a centromere, almost never survives, and thus many genes are lost.
Inversions occur when there are two interstitial breaks in a chromosome, and the segment reunites after a complete turnaround.
ring chromosome is a variant of a deletion. After loss of segments from each end of the chromosome, the arms unite to form a ring.
Chromosomal disorders may be associated with absence (deletion, monosomy), excess (trisomy), or abnormal rearrangements (translocations) of chromosomes.
In general, a loss of chromosomal material produces more severe defects than does a gain of chromosomal material.
Excess chromosomal material may result from a complete chromosome (as in trisomy) or from part of a chromosome (as in Robertsonian translocation).
Imbalances of sex chromosomes (excess or loss) are tolerated much better than are similar imbalances of autosomes.
Sex chromosomal disorders often produce subtle abnormalities, sometimes not detected at birth. Infertility, a common manifestation, cannot be diagnosed until adolescence.
In most cases, chromosomal disorders result from de novo changes (i.e., parents are normal, and risk of recurrence in siblings is low). The translocation form of Down syndrome (described later) exhibits an uncommon but important exception to this principle.