No abstract

Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta2m). The number of STR identified in the HLA region is still increasing. In this study, seven representative STR markers covering the 6p/6q arms of chromosome 6 including the HLA region and two for chromosome 15 flanking the beta2m gene, were selected as minimally required for reliable LOH studies. A multiplex polymerase chain reaction (PCR) strategy is proposed when small number of cells are available in microdissected tumor samples.

We have studied the allele distribution of DRB1, DQB1 and DPB1 loci in 80 unrelated Gypsies living in different eastern areas of the Andalusian province of Granada (southern Spain). The frequency distribution of HLA class II alleles and the genetic distance of Andalusian Gypsies from several Caucasian populations indicate a marked similarity - but not total - of the former with the Gypsy population previously studied in Madrid (central Spain), which suggests that both groups migrated together out of India. In terms of genetic distance, both Gypsy groups are more like the Czech Gypsies and the Northern Indian groups than their neighbouring Caucasian non-Gypsy populations. In summary our data support the hypothesis of a common anthropological origin of all three European Gypsy groups, which probably split up after their arrival in Europe.

We evaluated the influence of the hereditary make-up on the development of systemic lupus erythematosus (SLE) in two ethnic groups [Gypsy and white Caucasian Mediterranean (WCM) populations], living in the same geographic area. We compared 81 WCM and 25 Gypsy patients with SLE. The control group consisted of 185 healthy unrelated individuals, 105 WC and 80 Gypsies. In the Gypsy population, the onset of SLE occurred at earlier ages than in the other ethnic group (25.9 versus 32.0 years, P = 0.02), and showed lower SLEDAI peak values (4.9 versus 7.0, P = 0.016). The frequency of joint, kidney, gastrointestinal and eye involvement was significantly lower in Gypsy patients. In contrast, SLE-associated antiphospholipid syndrome, thrombosis and livedo reticularis were more frequent in Gypsies than in the majority ethnic group (WCM). In WCM patients, DRB1* 1303-DQB1*0301 haplotype was associated with SLE (P = 0.001, Pc = 0.038). We found SLE to be associated with DR5 (P = 0.006, Pc = 0.05) in the Gypsy population as well as a protective effect of DPB1*0401 when DR5 was not present (P = 0.008, Pc = 0.032). In conclusion, we found some clinical differences between WCM and Gypsy patients with SLE. Furthermore, HLA associations between HLA-DRB1-DQB1 and SLE were different for Gypsy people.

Objective To evaluate the contributions of HLA–DQ and –DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II region's contribution to RA predisposition. Methods One hundred sixty RA patients and 153 healthy controls were typed for HLA–DRB1 and –DQB1 using high‐resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA‐positive DRB1 alleles according to the RAP model. Results DQ3 (DQB1*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE‐positive DRB1 alleles. DQ3/3‐homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB1*1001‐carrying haplotype; no DRB1*1001‐homozygous patients were observed. DRB1*0401 played a unique role in the contribution of DQ3–DR4 haplotypes to RA, in spite of its low frequency in southern Spain. Conclusion The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3–DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA–DQ and –DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.