Specific association of repetitive DNA sequences with major histocompatibility genes.

Abstract

The DNA sequence organization of a 17.8-kilobase segment of porcine DNA, containing a functional major histocompatibility (MHC) The major histocompatibility complex (MHC) in humans and other vertebrates encodes a series of highly polymorphic cell-surface glycoproteins involved in a variety of immunological phenomena (18,29). The transplantation antigens (class I) are of particular interest in that they are targets in, and restricting elements for, cytotoxic lymphocyte reactions (43) and are probably the major antigens involved in graft rejection. These antigens consist of two associated polypeptides, a heavy chain (45,000 daltons) and a light chain identified as b2-microglobulin. Genetic studies have shown that in each species there are a number of distinct loci within the MHC which encode class I heavy chains. Extensive serological (1,17) and biochemical analyses (24) of transplantation antigens, including detailed amino acid sequence determinations (6,25,38), have revealed that the heavy chains are highly polymorphic in humans, mice, and miniature swine. More than 50 different alleles at each locus have been identified in mice (18). Thus, the heavy chains of transplantation antigens represent one of the most polymorphic multigene families known in eucaryotes. The mechanisms generating this diversity are not known. In contrast, b2-microglobulin, which is not encoded in the MHC, is essentially invariant within a species.The genetic complexity, diversity, and biological importance of the MHC have provided the impetus for numerous studies contributing to the characterization of this complex in a variety of species. Recently, this analysis has been extended to an assessment of the DNA sequence organization of the MHC, and a variety of genes encoding MHC antigens from humans (20,26,32), mice (7,13,35), and miniature swine (30) have been isolated. It has been estimated that the number of sequences homologous to class I heavy-chain genes ranges from about 12 in swine (30) to approximately 40 in some strains of mice (35). To date, analysis of DNA sequences of MHC genes from both humans (20) and mice (35) reveals the common eucaryotic gene organization: separate exons encode the three external polypeptide domains and the transmembrane and cytoplasmic segments. Studies on the structure of the MHC class I genes have led to the proposal (13) that the extensive polymorphism observed in the MHC may in part be generated by gene conversions in addition to more well defined mechanisms, such as point mutations and recombination. However, it is apparent that analyses of structural genes alone will not totally elucidate the regulatory events leading to differential expression of MHC genes and the generation of polymorphism, nor will they reveal the evolutionary processes occurring within the MHC.Another approach is to examine the organization and structure of DNA sequences linked to MHC genes. In mice the intergenic distances range from less than 10 kilobases (kb) to greater 903 on May 9, 2018 by guest

Heterochromatic and genetic features are consistent with recombination suppression of the self‐incompatibility locus in Antirrhinum

“…, 1999). Furthermore, the mating‐type locus in yeast is heterochromatic (reviewed by Haber, 1998), and the major histocompatibility complex (MHC) locus in mammals is probably heterochromatic, with repetitive sequences and low recombination levels (Singer et al. , 1983; Walsh et al.…”

Assignment of the porcine major histocompatibility complex to chromosome 7 by in situ hybridization

“…To test this hypothesis, 125I-PD1A, an SLA class I specific recombinant DNA probe (Singer et al, 1983) was hybridized to chromosomes of two porcine fibroblast cell lines (ETH3 and ETH21) known to carry defined chromosome 15 rearrangements. Strategies have been reported for mapping chromosomal loci by in situ hybridization to metaphase spreads of cells having diagnostic marker chromosomes (Barker et al, 1984;Emanuel et al, 1984).…”

Differential expression of porcine major histocompatibility DNA sequences introduced into mouse L cells.

“…The BamHI-HindlII 4.2-kb fragment containing MHC homologous sequences (PD1A) and BamHI-BamnHI fragments 5-1, C12, Cll, B-5, 6-1, and 7-9 of PD1 (see Fig. 2) were subcloned into plasmid pBR322 (29). Whole plasmids or purified inserts (48) (as indicated in the figure legends) were labeled with 32P by nick translation (18) exogenous pig sequences were transcribed in the L cells or a differential transcription of the MHC sequences existed was next examined.…”

“…The remainder of the DNA segment contains members of different genomic families of moderately and highly repetitive DNA (29). In this paper, we have investigated the transcription and chromatin organization of the pig MHC DNA segment introduced into mouse L cells.…”