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  • Title: Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships.
    Author: Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M.
    Journal: Genomics; 1996 Jan 01; 31(1):95-106. PubMed ID: 8808285.
    Abstract:
    Defensins, a family of antimicrobial peptides isolated from several mammalian species, have a proposed functional role in innate host defense. In humans, certain defensin genes are expressed in phagocytic cells of hematopoietic origin, while others are expressed in Paneth cells, epithelial cells of the small intestine. In this study, we determined the chromosomal localization of the human defensin (HD) genes expressed in Paneth cells, HD-5 and HD-6. Analysis of a panel of human/hamster hybrids localized both HD-5 and HD-6 to chromosome 8. Southern blot analysis of DNA from cell lines that contain either chromosome 8 deletions or duplications further localized these two genes to 8p21-pter. Fluorescence in situ hybridization analysis of metaphase chromosomes using an HD-5 probe further supported the regional map assignment. Previous studies had localized the hematopoietic genes to chromosome 8p23, and the current work is consistent with both the enteric and the myeloid defensin genes being located at the same cytogenetic region of chromosome 8. In addition, the evolutionary relationships of this gene family were addressed using dot matrix sequence analysis. From this analysis, a model for the possible evolutionary history of the human defensin genes is proposed. According to this model, an early duplication of a primordial defensin gene yielded the ancestral genes of present day HD-5 and HD-6. The model further suggests that a subsequent unequal meiotic crossover event had generated an additional gene, comprised of a hybrid of sequences from the two parental genes, and that this hybrid gene then served as the ancestor to present day hematopoietic defensin genes.
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