Chromosomal Genetic Disease: Structural Aberrations


Structural chromosome rearrangements are changes in the physical structure of chromosomes that may result in birth defects, mental retardation and increased risk for infertility or pregnancy loss.

Keywords: cytogenetics; inversions; insertions; deletions; duplications; isochromosomes; ring chromosomes; aneusomy; karyotype; contiguous gene syndromes; reciprocal translocations; robertsonian translocations; quadrivalent

Figure 1.

Formation of structural rearrangements.

(a) Terminal deletion: formation of a terminal deletion by a single break with loss of the terminal segment.

(b) Ring: formation of a ring chromosome by a break in each arm, loss of the terminal segments and union of the centric segment.

(c) Interstitial deletion: formation of an interstitial deletion by two breaks in the same arm, loss of the interstitial segment, and reunion of the two remaining segments.

(d) Duplication/deletion: formation of a direct duplication and a deletion from unequal crossing‐over.

(e) Reciprocal translocation: formation of a reciprocal translocation by a break in each chromosome and exchange of the noncentric segments.

(f) Robertsonian translocation: formation of a Robertsonian translocation by a break within the centromere of each chromosome, union of the two long arms and loss of the two short arms, reducing the chromosome number by one.

(g) Pericentric inversion: formation of a pericentric inversion by a break in each arm, 180° rotation of the centric segment, and reunion of the terminal segments with the centric segment.

(h) Paracentric inversion: formation of a paracentric inversion by two breaks in the same arm, 180° rotation of the interstitial segment, and reunion of the terminal segments with the interstitial segment.

Figure 2.

Segregation patterns from reciprocal and Robertsonian translocations. After Hirschhorn .

(a) Reciprocal translocation: a pachytene quadrivalent is shown with the results of alternate, adjacent I, adjacent II and 3 : 1 segregation, and fertilization by a normal gamete. Note that only one of the four possible combinations is represented for 3 : 1 segregation.

(b) Robertsonian translocation: a pachytene quadrivalent is shown with the results of the six possible segregation patterns and fertilization by a normal gamete.

Figure 3.

Pairing and crossing‐over within an inversion loop formed by (a) pericentric and (b) paracentric inversion heterozygotes, resulting in abnormal chromatids with duplications and deficiencies. Note that only two of the four chromatids participate in a single cross‐over event. After Srb et al. .



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Further Reading

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

Ledbetter DH and Ballabio A (1995) Molecular cytogenetics of contiguous gene syndromes: mechanisms and consequences of gene dosage imbalance. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, pp. 811–839. New York: McGraw‐Hill.

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Therman E and Susman M (1993) Human Chromosomes. Structure, Behavior, and Effects, 3rd edn. New York: Springer.

Vogel F and Motulsky AG (1997) Human Genetics. Problems and Approaches, 3rd edn. Berlin: Springer.

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Moore, Charleen M, and Best, Robert G(Apr 2001) Chromosomal Genetic Disease: Structural Aberrations. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0001452]