A continuous restriction map from HLA-E to HLA-F. Structural comparison between different HLA-A haplotypes

Abstract

The class I region of the human major histocompatibility complex contains genes encoding the classical transplantation antigens (HLA-A, B, and C), at least three new class I genes (HLA-E, F, and G) and many class I pseudogenes (including HLA-H). By pulse field gel electrophoresis and using five rare cutter enzymes, we have constructed a precise and continuous map of 1200 kilobases (kb) around HLA-A. The blots were hybridized with HLA-A, E, and F-specific probes and with new probes derived from yeast artificial chromosomes and cosmids of the class I region. We have compared the genomic organization of the same 1200 kb in three homozygous lymphoblastoid cell lines corresponding to three different HLA haplotypes (A3, A24, and A31). The differences in size observed may have been caused by insertions and deletions and may prove valuable in understanding the evolution of the HLA chromosomal region.

Coevolution of PERB11 (MIC) and HLA Class I Genes with HERV-16 and Retroelements by Extended Genomic Duplication

“…Diversity within the genomic sequence of the alphablock is confirmed by the report of a 40-50-kb deletion between HLA-A and HLA-G in human haplotype HLA-A9 (Vendetti et al 1992) and HLA-A24 (Watanabe et al 1997) and an insertion of 70 kb in a region between HLA-J and PERB11.4 in human haplotypes HLA-A30, -A31, and -A33 (El Kahloun et al 1992;Watanabe et al 1997). Whether these indels are inherited from nonhuman primates or are recent occurrences specific to humans is not known.…”

Inactivation of a functional HLA-A gene: A 4-kb deletion turns HLA-A*24 into a pseudogene

“…All fragments were successfully amplified by PCR, except fragments 4 and 5 of individual II-2, who is homozygous for A*24:02:01. A 50-kb deletion encompassing these fragments has previously been described for A*24:02 homozygous individuals [33]. Also the homozygosity of these fragments in individuals II-4 and II-5 can be ascribed to the presence of HLA-A*24:02:01 on one of the haplotypes.…”

?Both man & bird & beast?: comparative organization of MHC genes

“…Many of the genes in the MHC have been found serendipitously, after the DNA encompassing them was cloned. A common method is to radioactively label genomic fragments and to screen cDNA libraries, zoo blots, or northern blots for expressed sequences, after competing out repetitive DNA Trowsdale et al 1990; E1 Kahloun et al 1992;Vernet et al 1993). Many of the MHC genes discovered were not near Htf islands.…”

“…It has been extensively studied because it controls resistance to neoplastic diseases of viral origin (Pazderka 1975;Plachy et al 1992). Antibodies defined three loci, B-F-and B-L-encoding molecules homologous to class I and class II, respectively, and B-G, encoding the highly polymorphic IV antigens which were initially red blood cell antigens, originally defined by alloantisera, but which in fact have a rather wide tissue distribution (Kahloun et al 1991;Kaufman et al 1991;Kaufman and Salomonsen 1992). There is no mammalian equivalent of the B-G gene cluster, the class 1V region, although interestingly, a mammalian gene in the class I region, MOG, has similarities to B-G antigens as well as to cattle butyrophilin, a gene that is expressed in the mammary glands during lactation (Steinman 1993).…”