HLA-C Research Articles

CpG islands and HTF islands in the HLA class I region: investigation of the methylation status of class I genes leads to precise physical mapping of the HLA-B and -C genes.

We have investigated the accessibility of the 5' CpG rich sequences (CpG islands) present in the 5' region of most if not all HLA class I genes to methylation sensitive rare cutter enzymes. We show that for HLA-A, -B, -C genes and a few other (but not all) class I sequences these CpG islands are unmethylated and therefore constitute HTF islands (CpG rich, unmethylated regions of DNA, usually associated with expressed genes). We then map precisely the HTF islands of the HLA-B and HLA-C genes and determine that they are separated by 130 Kb (in agreement with genetic data) and that these two genes are in the same transcriptional orientation on the chromosome.

Another HLA‐B/C Recombination

Another case of an HLA-B/HLA-C recombination is presented which shows that the locus HLA-C is situated between HLA-A and HLA-B.

The HLA system in Italy.

4,902 Italians were typed for HLA-A antigens, 4,721 for HLA-B and 1,503 for HLA-C. The samples, which were composed of unrelated, healthy individuals born in Italy, were used for estimating HLA-A, HLA-B and HLA-C gene frequencies with the maximum-likelihood method. Different Italian regions showed significant differences in the HLA alleles, providing further evidence for the genetic heterogeneity of the Italian population. HLA gene frequencies place continental Italy and Sicily in a position which is similar to that of other Mediterranean populations, whereas the genetic isolation of Sardinia is quite evident. The most significant linkage disequilibrium values found in the Italian population (except for Sardinia) were in agreement with those observed in other Caucasian populations. The difference between Northern and Southern Italy and between continental Italy and Sardinia was emphasized by the linkage disequilibrium values and by the principal-component analysis as well.

Comparison of HLA class I gene sequences. Derivation of locus-specific oligonucleotide probes specific for HLA-A, HLA-B, and HLA-C genes.

The major histocompatibility complex in man contains at least 20 class I genes. Included within this family are three closely linked loci with 11-47 codominant alleles that encode the classical transplantation antigens HLA-A, -B, and -C. The study of individual HLA-A, -B, and -C genes is complicated both by the high degree of sequence homology among all members of the class I gene family and by the high degree of polymorphism exhibited by HLA-A, -B, and -C genes. Identification of potential locus-specific regions suitable for use as unique probes has been limited by the small number of nucleotide sequences available for comparison. In the present study, the nucleotide sequences of two cDNA clones, designated HLA-4 and HLA-10, that encode previously unsequenced alleles of HLA-C and HLA-A genes, respectively, are compared with those of other class I genes. From these intergenic and interallelic comparisons, it was deduced that the nucleotide sequence encoding amino acids 291-299 of the transmembrane region showed sufficient divergence between loci and similarity between alleles, to be suitable for the generation of locus-specific probes. Synthetic oligonucleotides were generated and shown to be highly locus-specific in hybridization. These probes were used successfully for the quantitation of the relative amounts of mRNA transcribed in human liver from HLA-A, -B, and -C genes; they should greatly simplify future studies of restriction fragment length polymorphisms of HLA-A, -B, and -C alleles as genetic markers of disease susceptibility.