Different patterns of A*80:01:01:01 allele generation based on exon or intron sequences.

Generation of the HLA-A*80:01:01:01 allele has been analysed using its complete sequence. Direct comparison of the sequences and phylogenetic trees using the human leukocyte antigen (HLA)-A representative alleles and the major histocompatibility complex (MHC)-A sequences of non-human primates has been made. Results based on exon sequences confirm previously published, but considering only the sequences of the introns, two distinct regions can be differentiated. The first one comprises from the 5' untranslated region region to the first part of intron 3 sequence (shared with A2 family), and the second one includes the sequence from the end of intron 3 to intron 7 (shared with A1/A3/A11/A36/A30 family). Each of them clusters with Gorilla and Chimpanzee MHC-A sequences, respectively, suggesting an origin coming from a common ancestor to Gorilla and Chimpanzee.

Identification of the novel HLA-DQB1*03:03:02:04 allele in a Spanish individual.

HLA-DQB1*03:03:02:04 and DQB1*03:03:02:02 alleles differ by a single point mutation in intron 2.

The novel HLA-G*01:03:01:02 allele differs from G*01:03:01:01 by a possible inversion event in intron 3.

HLA-G*01:03:01:02 and G*01:03:01:01 differ by a two nucleotide changes in intron 3.

HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles.

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I-class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1-DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.

The HLA-B*83:01 allele is generated by a gene conversion event including whole of exon 2 and partial introns 1 and 2 between B*44 and B*56 alleles.

Several studies have indicated the gene conversion as the most important mechanism about the MHC polymorphism generation when intron sequences are studied. The data obtained confirm that the B*83:01 allele is generated by gene conversion event including exon 2 and partial intron 1 and 2 between B*44 and B*56 alleles.

A new allele, HLA-G*010120, is generated by a recombination event between HLA-G*01010101/02 and HLA-G*01010201.

Recombination between HLA-G*01010101/02 and HLA-G*01010201 generates HLA-G*010120.

A new allele, HLA-G*01010106, with changes in intron 2.

Three nucleotide changes and one insertion in intron 2 upon human leucocyte antigen (HLA)-G*01010105 generate HLA-G*01010106.

The novel HLA-G*01010302 allele differs from G*01010301 by a single nucleotide change in intron 5.

HLA-G*01010301 and G*01010302 differ by a single point mutation in intron 5.

North African-Mediterranean HLA genetic contribution in a population of the kidney transplant waiting list patients of Canary origin (Gran Canaria).

The peopling of the Canary Islands has been widely debated. The mitochondrial DNA and Y-chromosome data support the idea of a Berber genetic origin coming from the North of Africa (maternal) and a later contribution of the Spanish invaders (paternal). The frequencies of the HLA class II alleles from the Tenerife Island (another Canary Island) have previously been published, postulating a Berber and Atlantic/Iberian contributions to the current population. The HLA class I and class II allele frequencies, haplotype frequencies and phylogenetic comparisons were performed in 215 unrelated individuals from Gran Canaria Island (belonging to the kidney transplant waiting list), with at least three generations of ancestors from Canary Islands, in order to study the different ethnical HLA contributions to the genetic background of the Canary Islanders. Results showed the presence of a compound HLA haplotype of putative Phoenician-Berber origin, A*33:01-C*08:02-B*14:02-DRB1*03:01-DQB1*02:01, likely coming from the combination of haplotypes A*30:02-C*05:01-B*18:01-DRB1*03:01-DQB1*02:01 and A*33:01-C*08:02-B*14:02-DRB1*01:02-DQB1*05:01 of North African (probably Berber) and West Asian Mediterranean (probably Phoenician) origins, respectively. The latter haplotypes and others from the same origin (Berber/Phoenician) are also present in the population studied. Besides, other contributions from the North of Europe, North England-Iberian (Atlantic contribution), and Western Europe/Mediterraneans (Spanish colonization) are also discussed. These data conclude that the current genetic background of the Canary Islands inhabitants has been generated over the years by different ways with an original Phoenician-Berber substrate and several genetic contributions generated in different invasions.

Description of the novel HLA-DQB1*02:02:01:02 allele in a Spanish individual.

HLA-DQB1*02:02:01:02 has an intron sequences coming from a combination of DQB1*02:01:01 and DQB1*02:02:01:01.

Description of the novel HLA-DQB1*02:02:01:02 allele in a Spanish individual.

HLA-DQB1*02:02:01:02 has an intron sequences coming from a combination of DQB1*02:01:01 and DQB1*02:02:01:01.

Exon-2 nucleotide sequences, polymorphism and haplotype distribution of a new HLA-DRB gene: HLA-DRB sigma.

Two new allelic exon-2 HLA-DRB sequences have been identified by using universal and also specific DRB primers. They may correspond to a previously unidentified DRB gene (DRB sigma) and define a new supratypic group ("DRw54") which includes DR1, DR"Br", DR2 and DRw10 bearing HLA haplotypes. This is probably the last HLA-DRB gene to be described in the standard DR haplotypes on the bases of the number of TaqI RFLPs obtained. Sequence comparison with their respective DP and DQ sequences shows that DRB sigma is unequivocally placed within the DRB family and also a constructed "neighbouring homology tree" indicates that DRB sigma gene is probably the eldest in the DRB family, thus the first to diverge from the ancestral DRB gene. An hypothetically deduced DRB sigma beta 1 protein domain was found to be quite different from the corresponding DRB1, DRB3, DRB4 and DRB5 products, since residues 40-55 would bear a longer alpha-helical conformation and would also exist a loss of both the extended conformation at residues 50-54 and the alpha-helix at residues 64-71. Thus, the putative DRB sigma protein would be remarkably different to other DRB ones. Also, a DRB sigma partial transcript (exon-2) has been obtained by PCR of cDNA by using specific DRB sigma oligonucleotides, but a specific Northern blot hybridization has not been achieved.

An Eco RI polymorphic site in the human complement C4 gene distinguishes juvenile rheumatoid arthritis (JRA) susceptibility-bearing haplotypes.

Susceptibility to acquire Juvenile Rheumatoid Arthritis (JRA) is linked to HLA-DR5 and DRw8 antigens in Caucasoid populations. However, the frequency of HLA-DR5 is too high in the normal Spanish population and JRA cannot thus be found to be associated with this antigen. It has been found a 14.3 kb-C4-Eco RI restriction fragment length polymorphism which correlates significantly with JRA and may be used as a marker for this disorder in Spaniards.

Autoimmunogenic HLA-DRB1*0301 allele (DR3) may be distinguished at the DRB1 non-coding regions of HLA-B8,DR3,Dw24 and B18,DR3,Dw25 haplotypes.

A novel TaqI restriction fragment length polymorphism (RFLP) of 4.15 kb is reported using a DR beta probe (pRTV1). This fragment corresponds to the DRB1 locus and allows the subdivision at the DNA level of the DRB1*0301 allele (DR3 antigen), which had not previously been reported. Both splits also distinguish each of the two DR3-bearing extended haplotypes (HLA-B8,SCO1,DR3,DQw2,Dw24 and B18,F1C30,DR3,DQw2,Dw25) found associated to several autoimmune diseases as insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and myasthenia gravis. The fact that no polymorphism in the DRB1*0301 coding DNA sequence has been detected indicates that DRB1*0301 intronic, regulatory of neighbouring sequences might also contribute to differential disease associations (and pathogenic mechanisms) found linked to each of the two DR3-bearing haplotypes, i.e. IDDM and B8,DR3,Dw24 in North European/American Caucasoids vs IDDM and B18,DR3,Dw25 in Mediterraneans; SLE and B8,DR3,Dw24 in children vs SLE and B18,DR3,Dw25 in Spanish adults.

Exon 2 DNA sequence of the HLA-DRw13b allele obtained from genomes of five different individuals.

Exon 2 nucleotide sequence of the DRB1 gene encoding the HLA-DRw13b allele defined by DNA-RFLP (Restriction Fragment Length Polymorphism) typing, has been obtained by using five heterozygous individuals genomic DNA and a non isotopic automated "dideoxi" methodology. Its comparison with other known homologous DRB1 sequences suggests that two different mechanisms which generate HLA allele variability may have occurred in this particular exon 2: a gene conversion between DRw11 or DRw13 as acceptors and DR4-Dw15 or DRw8.1 as donors and in addition, a non-conservative point mutation at base 221. The relationship between this HLA sequence characteristics and certain diseases susceptibility is discussed.

Lack of preferential transmission of diabetic HLA alleles by healthy parents to offspring in Spanish diabetic families.

HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. These results are discrepant with those found by others in families with diabetic parents in other ethnic groups. These conflicting data could be due to sampling errors or segregation distortion. Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. B8-DR3-BfS-C4AQOB1 and Bw62-DR3-BfS-C4A383 in most caucasians) but not for other haplotypes in other ethnic groups (Spaniards; B18-DR3-BfF1-C4A3BQO and BwX-DR4-BfX-C4AXBX).

Kaposi's sarcoma developing in a liver graft.

The case reported herein involved a patient who developed Kaposi's sarcoma (KS) in the liver graft, with severe liver disfunction and eventually the patient's death. This patient is our only KS case among the 7 neoplasias arising de novo (6 lymphoproliferative syndromes) in a series of 402 liver transplants (382 immunosuppressed with cyclosporine and prednisolone and 20 with FK-506 and prednisolone). The anatomic distribution of the KS in the autopsy study, and the HLA haplotypes typed in the donor and in the recipient, suggest that the KS arose in the stromal endothelial cells of the donor liver.

The correlation between languages and genes: the Usko-Mediterranean peoples.

The usko-Mediterraneans peoples are defined as ancient and present day populations that have lived in the Mediterranean/Middle-East/Caucasus area and have spoken a Basque related language. The present day existing populations show an HLA genetic relatedness which is more or less close according to geographical distance. The Greek sample is an outlying in all genetic analyses, because Greeks have a significant genetic input from sub-Saharan Ethiopians and Blacks. This probably occurred in Pharaonic times. Present day comparisons between genes and languages show a lack of correlation: Macedonian, Palestinians, Kurds, part of Berbers, Armenians, and Turks belong to the old Mediterranean substratum, but they do not speak a language included in the old Mediterranean Dene-Caucasian group. This is due to an "elite"-imposed culture and language. Other ethnic groups speak an "old Mediterranean language" or "usko-Mediterranean language" modified by Roman Latin (i.e., Spanish, Italians), or by other not fully explained processes (Jews). Therefore, the correlation between genes and languages may exist at a macrogeographical level, but not when more precise microgeographical studies are done, as shown in the present "usko-Mediterranean" peoples model.

Evolutionary relationships of HLA-DR8 alleles and description of a new subtype (DRB1*0806) in the Algerian population.

A new HLA-DR8 allele (HLA-DRB1*0806) found in the Algerian population is described here. This allele has an exon-2 nucleotide sequence identical to that of the HLA-DRB1*0801 allele, except for a GGT to GTG change in codon 86, yielding an amino acid substitution (glycine to valine). This change is also found in other HLA-DRB1 and HLA-DRB3 evolutionary-related allele pairs. HLA-DRB1*0806 is the most frequent HLA-DR8 allele found in this population (three of eight HLA-DR8-positive individuals) and is included within the HLA-DQA1*0102-DQB1*0602 haplotype (HLA-DQ6 serotype). This combination of HLA-DQ alleles is sporadically found associated with other HLA-DR8 alleles in other ethnic groups, i.e., HLA-DRB1*0804 in Bushmen and in North American blacks and HLA-DRB1*0803 in African blacks. Also, the HLA-DRB1*0806-DQ6 haplotype only bears one HLA-DRB gene copy, a common characteristic of the HLA-DR8 haplotype family. An exon-2 HLA-DR8 dendrogram has also been constructed with the available sequence data, indicating that this new allele does not seem to be placed at a distance significantly different from the origin to that of HLA-DRB1*0804 (proposed to be the eldest in the HLA-DR8 allele diversification pathway). A possible HLA-DR8 evolutive pathway is postulated according to the available exon-2 HLA-DR8 allele sequences.

Genetic variation among the Golla pastoral caste subdivisions of Andhra Pradesh, India, according to the HLA system.

The HLA allele frequency distributions have been characterized for the HLA class I and class II loci of the Golla pastoral caste, from Southeast India, subdivided into the subcastes (Puja, Punugu, Kurava, Pokanati, Karnam, and Doddi). Genetic distances, neighbor-joining, correspondence, and haplotype analyses all indicate that the subcastes exhibit a high haplotype variability and that their genetic substratum may be the result of European-Middle East/Asian admixture with the autochthonous populations. The Karnam subcaste seems to be the one that has undergone a higher degree of admixture, when compared with the other subcastes. The Golla speak an old Indian Dravidian language and should theoretically represent the basic Indian substratum that existed before the postulated "Aryan" invasion.