The chromosome region containing the highly polymorphic HLA class I genes displays limited large scale variability in the human population.

Chimini, Giovanna; Pontarotti, Pierre; Nguyen, Catherine; Toubert, Antoine; Boretto, Joëlle; Jordan, Bertrand

doi:10.1002/j.1460-2075.1988.tb02826.x

Cited by 27 publications

(14 citation statements)

References 28 publications

(24 reference statements)

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“…3), a distance consistent with that proposed by previous pulsed-field mapping experiments (1-3, 15, 16). As observed in studies using isolated cosmid clones, both loci are associated with CpG islands, with the islands marking the 5' end of each class I gene (15,16). Together with our data this indicates that each gene is located telomeric of these islands and transcribed in a centromeric-to-telomeric orientation.…”

supporting

confidence: 89%

Isolation and characterization of yeast artificial chromosome clones linking the HLA-B and HLA-C loci.

Bronson

Pei

Taillon-Miller

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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A 290-kilobase-pair chromosomal segment containing the genes encoding the human class I major histocompatibility complex molecules HLA-B and HLA-C as well as a class I pseudogene has been isolated on three overlapping yeast artificial chromosome (YAC) clones. One YAC clone contains both the HLA-B and HLA-C genes. These loci are located =85 kilobase pairs apart, each in close association with a CpG island. Southern blotting and nucleotide sequencing showed no evidence of alteration of the structure of the cloned DNA in the YACs. End fragments from the YAC inserts have been isolated and used to confirm the overlaps between clones. These fragments can also serve as polymorphic markers for structural analysis of the major histocompatibility complex. Our data show that YAC cloning offers an attractive alternative for analysis of the structures of large gene complexes such as HLA.

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supporting

confidence: 89%

Isolation and characterization of yeast artificial chromosome clones linking the HLA-B and HLA-C loci.

Bronson

Pei

Taillon-Miller

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Few probes were available for analysis of this region and were essentially the class I genes themselves or sequences very close to them. During a previous study on the structure of the HLA class I region, we found differences in the size of haplotype HLA-A24 (in relation to the other six that were tested; Chimini et al 1988). Similar reports have shown differences in size for haplotype A31 (Lord et al 1990).…”

Section: Introductionsupporting

confidence: 57%

“…Preparation of high relative mass DNA in agarose blocks from cultured cells, restriction digests, transfer onto nylon membranes, and hybridization were essentially as previously described (Carle and Olson 1984;Van Ommen and Verkerk 1986;Chimini et al 1988). Five rare cutter enzymes were used: Not I, Mlu I, Nru I, Sal I, and Sfi I in single or double digestion.…”

Section: Methodsmentioning

confidence: 99%

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

Kahloun¹,

Vernet

Jouanolle³

et al. 1992

Immunogenetics

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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.

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“…It contains more than 50 genes in about 4 million base pairs (bp) of DNA (1). The organization of the genes has been determined by a combination of techniques including recombination analysis, cosmid walking, and pulsed-field gel electrophoresis (PFGE) (2)(3)(4)(5). The telomeric end of the MHC contains the class I genes (6) and the centromeric end the class II genes (7).…”

mentioning

confidence: 99%

Cloning of the HLA class II region in yeast artificial chromosomes.

Ragoussis

Monaco

Mockridge

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Yeast artificial chromosomes (YACs) have been applied to clone the entire class II region of the human major histocompatibility complex (MHC), including its flanking regions, in a contig over 1.5 million base pairs (bp) long. The human DNA inserts in the YACs have a size between 60 and 1300 kbp and were isolated from two EcoRI partial digest libraries. The gaps between DRA and DRB, DRB and DQA, and DOB and DPA, which had not been cloned by other means, have been bridged with YAC clones. The contig extends through the 400 kbp of DNA between the DRA and C4 genes, thus linking the class II region with the complement gene cluster in the class III region. The cloning in YACs has been supported by a conventional cosmid walk of 290 kbp in the C4-DRA region. Restriction enzyme sites in the YAC clones were compared to the sites in the cosmid walk, to published cosmid clones, and to the already existing physical maps, leading to a detailed characterization of a region of the human genome over 1500 kbp. The YAC clones will be valuable for functional analysis of the MHC.The human major histocompatibility complex (MHC) is situated on the short arm of chromosome 6 in the 6p21.3 band. It contains more than 50 genes in about 4 million base pairs (bp) of DNA (1). The organization of the genes has been determined by a combination of techniques including recombination analysis, cosmid walking, and pulsed-field gel electrophoresis (PFGE) (2-5). The telomeric end of the MHC contains the class I genes (6) and the centromeric end the class II genes (7). The class I and class II gene products play a central role in immune responses by presenting antigens to T lymphocytes. The class III region, between class I and class II, contains a large number of genes encoding proteins of diverse functions such as the complement components C2 and C4 (8), steroid 21-hydroxylase (9), tumor necrosis factors a and /, and the heat shock protein HSP70 (3, 10, 11).The class II region is divided into the DR, DQ, and DP subregions, each of which contains at least one A and one B gene, encoding one a and one f class II protein chain, respectively. The organization of the class II genes has been analyzed in detail by PFGE, leading to the construction of physical maps (12-15). Differences in the maps between individual haplotypes have been revealed (16,17), in particular in the segment of DNA between the DQA and DRA genes (14). Differences have also been observed in the class III region due to the number and size of C4 genes present (18,19). Cosmids have been isolated from each of the class II subregions, but large uncloned gaps remain. In the DR subregion different groups have isolated cosmids containing DRA or DRB genes, but it was not possible to link all DRB genes with each other (20) or to DRA (21-23). The DQ subregion has been cloned (24), but it was not linked to DR or to the DNA gene (25). The DNA gene has not been linked to the DP subregion by cosmid walking (25). Similarly, the 400 kilobase pair (kbp) region between class II and the complemen...

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The chromosome region containing the highly polymorphic HLA class I genes displays limited large scale variability in the human population.

Cited by 27 publications

References 28 publications

Isolation and characterization of yeast artificial chromosome clones linking the HLA-B and HLA-C loci.

Isolation and characterization of yeast artificial chromosome clones linking the HLA-B and HLA-C loci.

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

Cloning of the HLA class II region in yeast artificial chromosomes.

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