Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats

Abstract

Familial growth hormone deficiency type 1A is an autosomal recessive disease caused by deletion of both growth hormone-1 (GH1) alleles. Ten patients from heterogeneous geographic origins showed differences in restriction fragment length polymorphism haplotypes in nondeleted regions that flanked GH1, suggesting that these deletions arose from independent unequal recombination events. Deoxyribonucleic acid (DNA) samples from nine of ten patients showed that crossovers occurred within 99% homologous, 594-base pair (bp) segments that flanked GH1. A DNA sample from one patient indicated that the crossover occurred within 454-bp segments that flanked GH1 and contained 274-bp repeats that are 98% homologous. Although Alu repeats, which are frequent sites of recombination, are adjacent to GH1, they were not involved in any of the recombination events studied. These results suggest that length and degree of DNA sequence homology are important in defining recombination sites that resulted in GH1 deletions.