Figure 9.17. Almost all 21-hydroxylase gene mutations are due to sequence exchange with a closely related pseudogene.

Figure 9.17Almost all 21-hydroxylase gene mutations are due to sequence exchange with a closely related pseudogene

The duplicated complement C4 genes and steroid 21-hydroxylase genes are located on tandem 30 kb repeats which show about 97% sequence identity. Both the C4A and C4B genes are expressed to give complement C4 products; the CYP21B gene (21B) encodes a 21-hydroxylase product, but the CYP21A (21A) gene is a pseudogene. About 25% of pathological mutations at the 21-hydroxylase locus involve a 30 kb deletion resulting from unequal crossover (UEC) or unequal sister chromatid exchange (UESCE). The remaining mutations are point mutations where small-scale gene conversion of the CYP21B gene occurs - a small segment of the CYP21A gene containing deleterious mutations is copied and inserted into the CYP21B gene replacing a short segment of the original sequence (see Figure 9.10C for one possible mechanism). Possibly gene conversion events are, like UEC and UESCE, primed by unequal pairing of the tandem repeats on sister or nonsister chromatids.

From: Chapter 9, Instability of the human genome: mutation and DNA repair

Cover of Human Molecular Genetics
Human Molecular Genetics. 2nd edition.
Strachan T, Read AP.
New York: Wiley-Liss; 1999.
Copyright © 1999, Garland Science.

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