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  • Title: Organization of C4 and CYP21 loci in gorilla and orangutan.
    Author: Kawaguchi H, Klein J.
    Journal: Hum Immunol; 1992 Mar; 33(3):153-62. PubMed ID: 1618655.
    Abstract:
    The standard human haplotype contains two C4 and two CYP21 loci arranged in the order C4A ... CYP21P ... C4B ... CYP21 and intercalated between the class I and class II loci of the HLA complex. The C4A gene is 22 kilobases (kb) long; the C4B gene is either 22 kb or 16 kb long. The CYP21P is a pseudogene characterized by an eight base pair (bp) deletion in exon 3 and other defects; the CYP21 is a functional gene. The standard chimpanzee haplotype is arranged in the same way as the standard human haplotype, except that both C4 genes are of the short variety; like the human gene, the chimpanzee CYP21P gene contains the 8 bp deletion. In the present study we demonstrate that a representative gorilla haplotype also consists of two short C4 genes and two CYP21 genes, neither of which, however, has the characteristic 8 bp deletion. On the other hand, the single characterized orangutan haplotype is organized in the following way: C4A ... CYP21 ... C4A ... CYP21 ... C4B ... CYP21. The first two C4 genes are of the long variety, the third gene is short. None of the defects characterizing the human CYP21P gene is present in any of the three orangutan genes. These conclusions are based on the analysis of overlapping clones isolated from cosmid libraries of the indicated species. The observed haplotype organization of the four primate species can be explained by expansion and contraction of the C4-CYP21 region through unequal homologous crossing-over, which preserves the differentiation of the C4 genes into the A and B categories but otherwise homogenizes these genes, as well as the CYP21 genes, within a given species. The 8 bp deletion in the CYP21P gene is postulated to have occurred before the separation of the lineages that led to modern humans and chimpanzees, but after the separation of these two lineages from the lineage that led to modern gorillas. The 6 kb insertion generating the long C4 gene is postulated to have occurred before the separation of the orangutan, gorilla, chimpanzee, and human lineages.
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