Juan Moscoso

HLA genes in the Chuvashian population from European Russia: admixture of Central European and Mediterranean populations.

HLA alleles have been determined for the first time in individuals from the Chuvashian population by DNA typing and sequencing. HLA-A, -B, -DR, and -DQ allele frequencies and extended haplotypes have also been determined, and the results compared to those for Central Europeans, Siberians and other Asians, Caucasians, Middle Easterners, and Mediterranean peoples. Genetic distances, neighbor-joining dendrograms, and correspondence analysis have been performed. Present-day Chuvash speak an Altaic-Turkic language and are genetically related to Caucasians (Georgians), Mediterraneans, and Middle Easterners, and not only to Central or Northern Europeans; Chuvash contain little indications of Central Asian-Altaic gene flow. Thus, present-day Chuvash who speak an Altaic-Turkic language are probably more closely related to ancient Mesopotamian-Hittites and northern European populations than to central Asia-Altaic people.

HLA genes in Uros from Titikaka Lake, Peru: origin and relationship with other Amerindians and worldwide populations

Uros population from the Titikaka Lake live in about 42 floating reed (‘totora’) islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour‐joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA‐A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA‐B, HLA‐DRB1 and HLA‐DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA‐B*4801 and HLA‐DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA‐A*680102‐B*3505‐DRB1*0403‐DQB1*0302; HLA‐A*2402‐B*1504‐DRB1*1402‐DQB1*0301; and HLA‐A*2402‐B*4801‐DRB1*0403‐DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

Different evolutionary pathway of B*570101 and B*5801 (B17 group) alleles based in intron sequences.

AbstractTwo theories about MHC allele generation have been put forward: (1) point mutation diversification and/or (2) gene conversion events. A model supporting the existence of both of these mechanisms is shown in this paper; the possible evolution of the HLA-B*570101 and HLA-B*5801 alleles (which belong to the HLA-B17 serology group) is studied. The hypothesis favoured is that gene conversion events have originated these alleles, because intron sequences are also analysed. Evolution by point mutation should only be accepted if flanking introns have also been sequenced.

Mitochondrial DNA Phylogenetic Definition of a Group of 'Arid-Zone' Carduelini Finches

Birds included within the Carduelini tribe (genera Rhodopechys, Carpodacus and Leucosticte) apparently be- long to the same radiation according to molecular phylogenetic analyses. Our phylogenetic analyses based on nucleotide sequences of the cytochrome b gene (cyt-b) indicate that some of these birds (Rhodopechys mongolica, R. githaginea and Carpodacus nipalensis) do not cluster together with their respective phenetically defined allies. This new group of birds thrives in both hot and cold arid zones and are phenetically distinct, probably because of their adaptation to different ex- treme environments. Both maximum likelihood and Bayesian inference methods support the existence of this new evolu- tionary basal group among finches which might have originated about 14 million years ago.

Different Evolution of Inhibitory and Activating Killer Immunoglobulin Receptors (KIR) in Worldwide Human Populations

HLA class I molecules are ligands for natural killer cells’ inhibitory (KIR DL) and activating (KIR DS) receptors. KIR DL receptors have a greater avidity for HLA class I molecules than KIR DS receptors. Thus, there is a possibility that HLA molecules drive KIR receptor selection. We have used the percentage of individuals bearing the genes KIR 3DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DL1, 2DL2, 2DL3, 2DL5 and 3DL1 in relatively well defined populations to test whether there is a different way of relating worldwide populations between KIR DS and KIR DL molecules. We h ave use d A RLEQUIN, D ISPAN and V ISTA computer p rograms t o c onstruct d endrograms a nd correspondence analyses showing the genetic relationships among different human world populations. Analyses based on KIR DS or KIR haplotype B ge nes show that populations are re lated according to geography, l ike a good a nthropological m arker (i .e.: HLA or Y chromosome systems). The results based on KIR DL or KIR haplotype A genes do not show such a correlation. Results are discussed taking into account the linkage of both HLA and KIR systems to microbial diseases and the possible evolutionary shaping of both HLA and KIR receptors repertoire by pathogens.

The evolution of the MHC-G gene does not support a functional role for the complete protein.

Summary: The study of the MHC‐G gene evolution during nearly 40 million years does not support a role for the full molecule. The MHC‐G‐like proteins of New World monkeys are probably classical presenting molecules. Old World Cercopithecinae monkeys do not have a full MHC‐G molecule and human individuals homozygous for the HLA‐G null allele are healthy and do not show birth pathologies.

Human leukocyte antigen haplotypes and HFE mutations in Spanish hereditary hemochromatosis and sporadic porphyria cutanea tarda

Background and Aims:  It has been postulated that the HFE C282Y mutation (linked to human leukocyte antigen [HLA]‐A3‐B7 haplotype) is not only responsible for hereditary hemochromatosis; HLA class I alleles would also contribute to the disease pathogenesis. In addition, H63D mutation linked to HLA‐A29‐B44 would also be pathogenetic, particularly in the Mediterranean Basin and throughout the world. However, sporadic porphyria cutanea tarda (s‐PCT) has also been linked to these HFE mutations. In the present work, we have studied HFE mutations and HLA genes to test these hypotheses.

A novel allele, HLA-G*010114, with a non-coding DNA base change in exon 2.

The non-classical human leucocyte antigen (HLA) class I locus, HLA-G, shows a low protein polymorphism and a more varied DNA (eight proteins and 28 alleles). HLA-G DNA polymorphism accounts mainly for changes at third codon bases of the protein coding exons; this does not imply amino acid change in most cases. This relatively high HLA-G DNA polymorphism in comparison with their protein polymorphism suggests that evolutionary forces are acting upon HLA-G for invariance. This may be related to the immunotolerogenic function postulated for HLA-G.

The peopling of Madeira archipelago (Portugal) according to HLA genes

The Madeira‐Porto Santo Archipelago was officially colonized in 1420 by Portuguese settlers. Its importance in Columbus’ information for the American discovery and for slave traffic across the Atlantic is unquestionable. Thus, a complex peopling may have given rise to a present‐day high admixture of ethnicities according to HLA genes. A sample of 173 healthy unrelated Madeirans was analysed and compared with 6986 HLA chromosomes from other worldwide populations. Genetic distances, neighbour‐joining dendrograms and correspondence analyses were used for comparisons. Southern European, North African (including Canary Islands), Jewish and Mediterranean typical HLA alleles were found and genetic distances from Madeirans to these populations were the closest ones. In addition A*24‐B*65‐DRB1*0102‐DQB1*0501 and A*68‐B*08‐DRB1*0301‐DQB1*0201 haplotypes were newly found in Madeira and not found in any other population. Jewish‐Armenian‐Middle East haplotype (A*33‐B*65‐DRB1*0102‐DQB1*0501) is one of the most common haplotypes; this haplotype is also present in Spaniards and North Africans. Quantitatively, Portuguese, North Africans (Algerians), Spaniards and Canary Islanders (in this order) are the most important parental populations to Madeirans. Results are discussed on the basis of the recorded historical peopling which does not show a noticeable African gene input in present‐day Madeiran population according to our data; one of the closest related populations found is the Canary Islanders, suggesting that Guanche (Canary Islands first inhabitants) slaves gene flow is still noticed at present, both in Madeira and in Canary Islands populations.

Rhodopechys obsoleta (desert finch): a pale ancestor of greenfinches (Carduelis spp.) according to molecular phylogeny

The evolutionary history of three out of four birds traditionally classified into the genus Rhodopechys birds has been studied by comparing their mitochondrial cytochrome b DNA sequence with that of greenfinches and other genus Carduelis finches. The desert finch (Rhodopechys obsoleta) or a sister extinct species seems to have existed about 6 million years ago in Asian and perhaps African desert-like areas. This bird has no molecular relationship with other Rhodopechys birds and seems to have given rise to the greenfinches radiation, probably by allopatry of marginal or isolated groups; the latter would have evolved to green plumage colours and more simple song modulations (i.e., greenfinches). The possible role of assortative mating and the newly postulated acquired phenotypic characters in greenfinches speciation are discussed.