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Unequal Crossing-Over Normally, DNA recombination in germ cells occurs with remarkable fidelity to maintain the precise junction sites for the exchanged DNA sequences (Fig. 62-3). However, mispairing of homologous sequences leads to unequal crossover, with gene duplication on one of the chromosomes and gene deletion on the other chromosome. A significant fraction of growth hormone (GH) gene deletions, for example, involve unequal crossing-over (Chap. 333). The GH gene is a member of a large gene cluster that includes a growth hormone variant gene as well as several structurally related chorionic somatomammotropin genes and pseudogenes (highly homologous but functionally inactive relatives. | Chapter 062. Principles of Human Genetics Part 15 Unequal Crossing-Over Normally DNA recombination in germ cells occurs with remarkable fidelity to maintain the precise junction sites for the exchanged DNA sequences Fig. 62-3 . However mispairing of homologous sequences leads to unequal crossover with gene duplication on one of the chromosomes and gene deletion on the other chromosome. A significant fraction of growth hormone GH gene deletions for example involve unequal crossing-over Chap. 333 . The GH gene is a member of a large gene cluster that includes a growth hormone variant gene as well as several structurally related chorionic somatomammotropin genes and pseudogenes highly homologous but functionally inactive relatives of a normal gene . Because such gene clusters contain multiple homologous DNA sequences arranged in tandem they are particularly prone to undergo recombination and consequently gene duplication or deletion. On the other hand duplication of the PMP22 gene because of unequal crossing-over results in increased gene dosage and type IA Charcot-Marie-Tooth disease. Unequal crossing-over resulting in deletion of PMP22 causes a distinct neuropathy called hereditary liability to pressure palsy Chap. 379 . Glucocorticoid-remediable aldosteronism GRA is caused by a rearrangement involving the genes that encode aldosterone synthase CYP11B2 and steroid 110-hydroxylase CYP11B1 normally arranged in tandem on chromosome 8q. These two genes are 95 identical predisposing to gene duplication and deletion by unequal crossing-over. The rearranged gene product contains the regulatory regions of 110-hydroxylase fused to the coding sequence of aldosterone synthetase. Consequently the latter enzyme is expressed in the adrenocorticotropic hormone ACTH -dependent zona fasciculata of the adrenal gland resulting in overproduction of mineralocorticoids and hypertension Chap. 336 . Gene conversion refers to a nonreciprocal exchange of homologous genetic information it is
