Immunobiology of HLA pp 73-75 | Cite as
Mapping of the Human Major Histocompatibility Complex by Pulsed Field Gel Electrophoresis
Abstract
Genetic analysis of recombinant HLA haplotypes in family studies has established that the class I loci (HLA-A, -B, and -C) lie telomeric to the class II (HLA-D) loci. Located between HLA-DR and HLA-B are the class III genes, encoding the serum complement proteins C2, Factor B, C4A and C4B as well as two copies of the steroid 21-hydroxylase (21-OHase) gene (1,2). The orientation and exact location of these genes relative to the class I and class II genes has not been determined due to the absence of informative recombination events. By a combination of cosmid walking and genomic mapping using pulsed field gel electrophoresis (PFGE) (3,4) we have derived a map of ~ 3800 kb of DNA covering the HLA region. This has allowed the position and orientation of the complement genes in the class III region to be defined, the C2 gene being telomeric to the C4 gene. In addition, the positions of the TNFα and β genes within the HLA region have been determined. They lie ~ 390 kb telomeric of the C2 gene and ~ 250 kb centromeric of the HLA-B locus.
Keywords
Complement Gene Human Major Histocompatibility Complex TNFa Gene Serum Complement Protein Single Restriction Enzyme DigestAbbreviations
- PFGE
pulsed field gel electrophoresis
- HLA
human leukocyte antigen
- MHC
major histocompatibility complex
- TNF
tumour necrosis factor
- kb
kilobase
- 21-OHase
steroid 21-hydroxylase.
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References
- 1.Carroll MC, Campbell RD, Bentley DR, Porter RR. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2, and factor B. Nature 1984; 307: 237–241.PubMedCrossRefGoogle Scholar
- 2.Carroll MC, Campbell RD, Porter RR. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci USA 1985; 82: 521–525.PubMedCrossRefGoogle Scholar
- 3.Schwartz DC, Cantor CR. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell 1984; 37: 67–75.PubMedCrossRefGoogle Scholar
- 4.Carle GF, Olson MV. Separation of chromosomal DNA molecules from yeast by orthogonal-field-alteration gel electrophoresis. Nucleic Acids Res 1984; 12: 5647–5664.PubMedCentralPubMedCrossRefGoogle Scholar
- 5.Yu CY, Campbell RD. Definitive RFLPs to distinguish between the human complement C4A/C4B isotypes and the major Rodgers/Chido determinants: Application to the study of C4 null alleles. Immunogenetics 1987; 25: 383390.Google Scholar
- 6.Dunham I, Sargent CA, Trowsdale J, Campbell RD. Molecular map of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci USA 1987; 84: 7237–7241.PubMedCrossRefGoogle Scholar
- 7.van Ommen GJB, Verkerk JMH. Restriction analysis of chromosomal DNA in a size range up to two million base pairs by pulsed field gradient electrophoresis. In: Davies KE (ed): Human genetic disease. A practical approach. Oxford, UK: IRL Press Ltd, 1986, pp. 113–133.Google Scholar
- 8.Hardy DA, Bell JI, Long EO, Lindsten T, McDevitt HO. Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature 1986; 323: 453–455.PubMedCrossRefGoogle Scholar
- 9.Spies T, Morton CC, Nedospasov SA, Fiers W, Pious D, Strominger JL. Genes for the tumor necrosis factors a and ß are linked to the human major histocompatibility complex. Proc Natl Acad Sci USA 1986; 83: 8699–8702.PubMedCrossRefGoogle Scholar
- 10.Müller U, Jongeneel CV, Nedospasov SA, Lindahl KF, Steinmetz M. Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature 1987; 325: 265–267.PubMedCrossRefGoogle Scholar
- 11.Nedospasov SA, Shakov AN, Turetskaya RL, Mett VA, Georgiev GP, Dobrynin VN, et al. Molecular cloning of human genes coding for tumour necrosis factor: Tandem arrangement of the alpha-and beta-genes in a short segment (6 kilobase pairs) of the human genome. Proc Acad Sci USSR (Dokl Acad Nauk SSSR) 1985; 285: 1487–1490.Google Scholar