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Background: Late-onset Alzheimer's disease (LOAD) is associated with changes in certain proteins, such as ApoE and Cyp46A1, of the elimination route for cerebral cholesterol. The main lipoprotein involved in its transport is ApoE whose 4 allele is the least efficient. However, the presence or absence of this allele does not determine the development of LOAD, which implies the existence of other susceptibility factors associated with the disease, such as the CYP46A1 gene that encodes the enzyme cholesterol 24S-hydroxylase. Objective: To find new data to contribute to the evaluation of whether the presence of the T allele in the polymorphic site rs754203 of the CYP46A1 gene leads to a greater risk of developing mild cognitive impairment (MCI) and LOAD. Furthermore, given the link between APOE and CYP46A1, we proceeded to relate both genotypes in each of the patient groups studied. Methods: We studied MCI and LOAD patients and also carried out an analysis of those MCI patients who progressed from a mild cognitive deterioration to a clinically evident Alzheimer's disease during the study. Results: The frequency of the CYP46A1-T allele in the LOAD patients with APOE3 alleles is significantly higher with respect to the control group; the same occurs in the group made up of LOAD patients together with the MCI patients who progressed to LOAD. The risk of developing LOAD when this allelic combination exists is 2.262 times higher (95% CI 1.337-4.202). However, having the CYP46A1-T allele does not increase the risk of suffering from LOAD in carriers of the APOE4 allele, probably because the transport of cholesterol is already affected in such patients and possibly masks the effect of the CYP46A1-T allele. Conclusions: The CYP46A1-T allele increases the risk of suffering from LOAD in persons carrying the APOE3 allele. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The single nucleotide polymorphism (SNP) -13910 C > T has proved a good predictor of the incidence of lactase persistence in Europe and South Asia. Yet, this is not the case in the Near East, although this region is a passageway between the two continents. Lactase persistence is associated with cattle breeding, which originated in the Fertile Crescent of the Near East and spread later during the Middle Neolithic throughout Europe. Here we analyzed five SNPs (-13915 T > G (rs41380347), -13910 C > T (rs4988235), -13907 C > G (rs41525747), -14009 T > G (rs869051967), and -14010 G > C (rs145946881)) in three Jordanian human groups, namely the Bedouins, Jordan valley farmers, and Jordanian urban people. The SNPs -14009 T > G and -14010 G > C were not detected in the sample, -13907 C > G was virtually non-existent, -13910 C > T showed low frequencies, and -13915 T > G exhibited salient frequencies. The estimated incidence of lactase persistence was lower in the urban population (16 %), intermediate in the Jordan Valley's farmer population (30 %), and higher among the Bedouins (62 %). In explaining our findings, we postulated climatic change brought about by the aridification episode of the Arabian Peninsula and the Sahara 4200 years ago. This climatic milestone caused the collapse of the Akkadian Empire and the Old Kingdom in Egypt. Also, it could have led to a drastic decline of cattle in the region, being replaced by the domestication of camels. Loss of traditional crops and increasing dependence on camel milk might have triggered local selective pressures, mainly associated with -13915 T > G and differentiated from the ones in Europe, associated with -13910 C > T., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The chromosomal region 17q21.31 harbors a 900 kb inversion polymorphism named after the microtubule-associated protein tau (MAPT) gene. Since no recombination occurs, two haplotypes are recognized: a directly oriented variant (H1) and an inverted variant (H2). The H2 haplotype features a distribution pattern with high frequencies in the Near East and Europe, medium levels in South Asia and North Africa, and low levels elsewhere. Studies of this genomic region are relevant owing to its likely association with numerous neurodegenerative diseases. However, the causes underlying the geographic distribution of the haplotype frequencies remain a bone of contention among researchers. With this work, we have intended to outline a plausible hypothesis on the origin of the high European H2 frequencies. To that end, we have analyzed an extensive population database (including three new Iberian populations) to explore potential clinal variations of H2 frequencies. We found a sigmoidal frequency cline with an upward trend from South Asia to Europe. The maximum value was detected in the Basques from Gipuzkoa province (0.494) with the curve's inflection point in the Near East. From our results, we suggest that the most likely scenario for high H2 frequencies in Europe would be a founding event in the Near East during the late Paleolithic or early Neolithic. Subsequently, such H2 overrepresentation would have reached Europe with the arrival of the first Neolithic farmers. The current frequencies and geographic distribution of the 17q21.31 inversion suggest that the founding events mainly affected the H2D subhaplotype., (© 2022. The Author(s).)

Frequencies of H1 and H2 haplotypes of the microtubule-associated protein tau (MAPT) gene were examined in two Jordanian samples. The criterion for haplotype assignment was the presence/absence of the intronic 238-bp deletion, located between exons 9 and 10 of the MAPT genomic region. We further compiled MAPT haplotype frequencies in Middle Eastern, South Asian, and European populations to widen the scope of analyses. Jordan MAPT*H2 haplotype frequencies peaked among worldwide samples analysed to date, with the Jordan general population featuring the top value (0.386). AMOVA tests results indicated spatial genetic structuring, as they unveiled significant differences in H2 frequencies between South Asia and Europe, with a hypothetical contact zone in the Middle East. The southeastern region of the Middle East shares low H2 frequencies with South Asia, while the northwestern area shows high H2 frequencies, similar to and even higher than observed in Europe. We suggest that high H2 frequencies could have originated at the beginning of the Neolithic in the western region of the Middle East, most likely through genetic drift episodes associated with founding events. Subsequently, the arrival of Neolithic farmers boosted the H2 haplotype spreading throughout Europe.

Objectives: This study aimed to explore the diversity of paternal lineages in Jujuy province (Argentina) by analyzing Y chromosome markers. Furthermore, we examined among-population genetic variability based both on paternally (NRY haplotypes) and maternally (mtDNA haplogroups) inherited markers. We sought to evaluate the impact of sex-biased gene flow on genetic background in Jujuy, and contribute data on the microevolutionary forces acting in this zone., Methods: DNA from 149 males from five Jujuy regions were analyzed for 12 non-recombining Y (NRY) markers. Genetic heterogeneity among Jujuy regions was evaluated through population differentiation tests. To identify potential genetic boundaries in Jujuy, analysis of molecular variance (AMOVA) and the Monmonier's algorithm implemented in the Barrier v2.2 software were employed., Results: A clear divergence between Jujuy highlands and lowlands for NRY haplotypes was found. A marked discrepancy between genetic structuring for paternal lineages and the lack of geographical pattern for mitogenomes was confirmed by all statistical analyses., Conclusions: Genetic structuring of paternal lineages is most likely caused by admixture processes that have occurred since colonial times in the Jujuy lowlands. Immigrants were predominantly male that settled in the lower altitude zones, due to the steep orography of the region. Input of allochthonous male lineages because of gene flow toward the lowlands would have increased diversity of NRY markers, thus compensating for drift effects. Likewise, limited input of allochthonous mitogenomes would have promoted genetic drift, a key factor in the shaping of diversity of maternal lineages across Jujuy subpopulations, irrespective of altitude., (© 2019 Wiley Periodicals, Inc.)

We examined tau haplotype frequencies in two different ethnical groups from the Basque Country (BC): Roma people and residents of European ancestry (general population). In addition, we analyzed the spatial distribution of tau haplotypes in Eurasian populations to explore the genetic affinities of the Romani groups living in Europe in a broader scope. The 17q21.31 genomic region was characterized through the genotyping of two diagnostic single nucleotide polymorphisms, SNPs (rs10514879 and rs199451), which allow the identification of H1 and H2 haplotypes. A significant heterozygous deficit was detected in the Romani for rs10514879. The H2 haplotype frequency proved to be more than twice in the BC general population (0.283) than in the Roma people (0.127). In contrast, H2 frequency proved to be very similar between Basque and Hungarian Romani, and similar to the H2 frequencies found in northwestern India and Pakistan as well. Several statistical analyses unveiled genetic structuring for the MAPT diversity, mirrored in a significant association between geography and genetic distances, with an upward trend of H2 haplotype frequencies from Asia to Europe. Yet, Roma samples did not fit into this general spatial patterning because of their discrepancy between geographical position and H2 frequency. Despite the long spatial coexistence in the Basque region between the residents of European ancestry and the Roma, the latter have preserved their Asian genetic ancestry. Bearing in mind the lack of geographical barriers between both ethnical groups, these findings support the notion that sociocultural mores might promote assortative matings in human populations.

This study explores potential signals of microdifferentiation in the gene pool of three high-altitude populations from Jujuy province in northwest Argentina using highly polymorphic markers. These human communities are characterized by extreme living conditions and very low population densities owing to considerable height above sea level and steep orography. A set of autosomal short tandem repeats (STRs) located at chromosome 6 (6p21.3) was typed in samples from Quebrada Baja (∼2,500 m), Quebrada Alta (∼3,300 m), and Puna (> 3,500 m). Genetic diversity was estimated through the observed and expected heterozygosities and the haplotype diversity. Analyses of the molecular variance (AMOVAs) and population differentiation tests based on allele and haplotype frequencies were performed to assess genetic heterogeneity among subgroups. No deviation from Hardy-Weinberg equilibrium was detected in any subpopulation, yet significant departures were detected in the analysis considering the whole area (D6S2792 and D6S105 loci). Overall, genetic diversity showed a decreasing trend as the altitude increased. Thus, allele and haplotype frequencies showed the most significant differences between Puna and Quebrada Baja, the populations sited at the edges of the altitude range. The trend toward reduction of heterozygosity with altitude is compatible with historical patterns of colonization, interregional migration trends, population density, and genetic admixture. The main consequence of the complex mountainous landscape of Jujuy would be an imbalance in the interplay of gene flow and genetic drift, favoring the latter. The combined effect of restricted gene flow and intense genetic drift would have promoted local genetic differentiation between the Jujuy highland subpopulations, leading to spatial patterning of the allele frequencies not entirely attributable to geographic distance. Our findings corroborate the effectiveness of STRs to identify microevolutionary changes.

Aims: To examine the role of genetic and environmental factors in the pathogenesis of alcohol dependence in a Spanish cohort of women and men., Methods: We analyzed the relationship between 56 genetic variants in 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption. The study sample (N = 1533, of which 746 were women) consisted of 653 heavy consumers and 880 very low consumers from the Spanish subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. Lifestyle variables were also examined to assess associations between genetic and environmental factors., Results: No statistically significant differences were found between cases and controls for the allele frequencies in five genes: TH, SLC18A2, DRD1, DRD3 and COMT. Conversely, some alleles of the 12 SNPs from the DRD2 locus and the 5 from the MAOA locus showed significant associations with excessive alcohol consumption. Namely, rs10891556 (DRD2) proved to be the only SNP positively correlated with excessive alcohol consumption in both sexes. DRD2 rs1800497 and rs877138 were significantly associated in men, whereas DRD2 rs17601612 and rs4936271 and MAOA rs5906898 were associated with excessive alcohol consumption in women. A correspondence analysis provided an overall lifestyle profile of excessive drinkers, who were predominantly men who smoked, had large intakes of meat, small intakes of fruit and vegetables, whose jobs did not require high education levels and who engaged in little physical activity., Conclusions: It has shown the influence of dopaminergic pathway in the genetics of alcohol dependence with differences between men and women and providing a lifestyle profile of excessive drinkers., (© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

The male genetic landscape of the territory currently known as Tunisia is hampered by the scarcity of data, especially from cosmopolitan areas such as the coastal city of Sousse. In order to alleviate this lacuna, 220 males from Sousse were examined, for the first time, for more than 50 Y-chromosome single-nucleotide polymorphisms (Y-SNPs) markers and compared with 3099 individuals from key geographically targeted locations in North Africa, Europe and the Near East. The paternal lineages observed belong to a common set of Y haplogroups previously described in North Africa. In addition to the prominent autochthonous North African E-M81 haplogroup which is exclusively represented by its subclade E-M183 (44.55% of Y-chromosomes), a number of Near Eastern Neolithic lineages including E-M78, J-M267 and J-M172 account for 39% of the Y-chromosomes detected. Principal component analysis based on haplogroup frequencies, multidimensional scaling based on Rst genetic distances and analyses of molecular variance using both Y-chromosome short tandem repeat haplotypes and Y-SNP haplogroup data revealed that the Tunisian and North African groups, as a whole, are intra- and inter-specific diverse with Sousse being highly heterogeneous.

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ~10,000 years before present (YBP), with signals of expansions at ~3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈ 15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈ 35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations.

Objectives: Genetic heterogeneity of two Amerindian populations (Jujuy province, Argentina, and Waorani tribe, Ecuador) was characterized by analyzing data on polymorphic Alu insertions within the human major histocompatibility complex (MHC) class I region (6p21.31), which are completely nonexistent in Native Americans. We further evaluated the haplotype distribution and genetic diversity among continental ancestry groups and their potential implications for the dating of the origin of MHC-Alus., Methods: Five MHC-Alu elements (AluMicB, AluTF, AluHJ, AluHG, and AluHF) were typed in samples from Jujuy (N = 108) and Waorani (N = 36). Allele and haplotype frequency data on worldwide populations were compiled to explore spatial structuring of the MHC-Alu diversity through AMOVA tests. We utilized the median-joining network approach to illustrate the continental distribution of the MHC-Alu haplotypes and their phylogenetic relationships., Results: Allele and haplotype distributions differed significantly between Jujuy and Waorani. The Waorani featured a low average heterozygosity attributable to strong population isolation. Overall, Alu markers showed great genetic heterogeneity both within and among populations. The haplotype distribution was distinctive of each continental ancestry group. Contrary to expectations, Africans showed the lowest MHC-Alu diversity., Conclusions: Genetic drift mainly associated to population bottlenecks seems to be reflected in the low MHC-Alu diversity of the Amerindians, mainly in Waorani. Geographical structuring of the haplotype distribution supports the efficiency of the MHC-Alu loci as lineage (ancestry) markers. The markedly low Alu diversity of African populations relative to other continental clusters suggests that these MHC-Alus might have arisen after the anatomically modern humans expanded out of Africa., (Copyright © 2013 Wiley Periodicals, Inc.)

Mitochondrial control region (16024-576) sequences were generated from 180 individuals of four population nuclei from the province of Jujuy (NW Argentina), located at different altitudes above sea level. The frequency at which a randomly selected mtDNA profile would be expected to occur in the general population (random match probability) was estimated at 0.011, indicating a relatively high diversity. Analysis of the haplogroup distribution revealed that Native American lineages A2 (13.9%), B (56.7%), C1 (17.8%), D1 (8.9%) and D4h3a (1.1%) accounted for more than 98% of the total mtDNA haplogroup diversity in the sample examined. We detected a certain degree of genetic heterogeneity between two subpopulations located at different points along the altitudinal gradient (Valles and Puna), suggesting that altitude above sea level cannot be ruled out as a factor promoting divergences in mtDNA haplogroup frequencies, since altitude is closely associated with human living conditions, and consequently, with low demographic sizes and the occurrence of genetic drift processes in human communities. In all, mitochondrial DNA database obtained for Jujuy province strongly points to the need for creating local mtDNA databases, to avoid bias in forensic estimations caused by genetic substructuring of the populations., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Polymorphic Alu insertions from the MHC class I region were analyzed in 215 autochthonous Basques from Guipuzcoa and Navarre provinces, with the aim of contributing new MHC Alu data in European ancestry populations. We also seek to assess both the genetic position of native Basques among worldwide samples and the efficiency of the MHC Alu elements as ancestry informative markers (AIMs). According to the MDS and AMOVA results, worldwide populations included in the comparative analyses were grouped in three major clusters defined by genetic ancestry (Africans, Asians and Europeans). The δ values (differences in weighted allele frequencies) among ancestry groups indicated that Alu elements within the alpha-block (AluHF, AluHJ and AluHG) showed an adequate resolving power to discriminate appropriately between some of the major ancestry groups. Alpha block Alu were also revealing of the exceptionality of Basques, as they allowed for the detection of genetic heterogeneity even between Basques and the other Iberian collection considered in the analysis (Valencia). Thus, analysis of the Alu loci within the alpha-block may represent a reliable, informative and cost-effective method to explore the ancestry, geographic origins and demographic history of human populations, which can be very helpful for studies into epidemiological, forensic or evolutionary perspectives., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

South America and especially the Amazon basin is known to be home to some of the most isolated human groups in the world. Here, we report on a study of mitochondrial DNA (mtDNA) in the Waorani from Ecuador, probably the most warlike human population known to date. Seeking to look in more depth at the characterization of the genetic diversity of this Native American tribe, molecular markers from the X and Y chromosomes were also analyzed. Only three different mtDNA haplotypes were detected among the Waorani sample. One of them, assigned to Native American haplogroup A2, accounted for more than 94% of the total diversity of the maternal gene pool. Our results for sex chromosome molecular markers failed to find close genetic kinship between individuals, further emphasizing the low genetic diversity of the mtDNA. Bearing in mind the results obtained for both the analysis of the mtDNA control region and complete mitochondrial genomes, we suggest the existence of a 'Waorani-specific' mtDNA lineage. According to current knowledge on the phylogeny of haplogroup A2, we propose that this lineage could be designated as subhaplogroup A2s. Its wide predominance among the Waorani people might have been conditioned by severe genetic drift episodes resulting from founding events, long-term isolation and a traditionally small population size most likely associated with the striking ethnography of this Amazonian community. In all, the Waorani constitute a fine example of how genetic imprint may mirror ethnopsychology and sociocultural features in human populations.

Two different sets of noncoding markers (microsatellites and Alu elements) from the human chromosome six were analysed in 106 individuals from Valencia (Spain), with the aim of exploring the effect of evolutionary forces on the genetic variability of the major histocompatibility complex (MHC) and assessing the potential usefulness of these genetic loci in phylogenetic studies. Linkage disequilibrium (LD) analyses revealed statistically significant associations among markers located in the MHC class I region, and also between the microsatellite D6S2792 and several genetic loci from MHC class I, II and III regions. Results of the Ewens-Watterson test indicated that only D6S2792 showed significant departure from selective neutrality. Despite the paucity of haplotype data in the literature, results of the phylogenetic analyses at world scale (Alu elements) showed that the genetic relationships of Valencia were mainly determined by the ethnic ancestry of the populations considered, whereas at European scale (microsatellites) population affinities were strongly influenced by geography. Our findings suggest that noncoding markers from the MHC such as Alu and microsatellite loci might have a potential value as lineage (ancestry) markers in investigations into evolutionary, medical and forensic perspectives., (© 2011 Blackwell Publishing Ltd.)

Objectives: The Amazon basin is inhabited by some of the most isolated human groups worldwide. Among them, the Waorani tribe is one of the most interesting Native American populations from the anthropological perspective. This study reports a genetic characterization of the Waorani based on autosomal genetic loci., Methods: We analyzed 12 polymorphic Alu insertions in 36 Waorani individuals from different communal longhouses settled in the Yasuní National Park., Results: The most notable finding was the strikingly reduced genetic diversity detected in the Waorani, corroborated by the existence of four monomorphic loci (ACE, APO, FXIIIB, and HS4.65), and of other four Alu markers that were very close to the fixation for the presence (PV92 and D1) or the absence (A25 and HS4.32) of the insertion. Furthermore, results of the centroid analysis supported the notion of the Waorani being one of the Amerindian groups less impacted by gene flow processes., Conclusions: The prolonged isolation of the Waorani community, in conjunction with a historically low effective population size and high inbreeding levels, have resulted in the drastic reduction of their genetic diversity, because of the effects of severe genetic drift. Recurrent population bottlenecks most likely determined by certain deep-rooted sociocultural practices of the Waorani (characterized by violence, internal quarrels, and revenge killings until recent times) are likely responsible for this pattern of diversity. The findings of this study illustrate how sociocultural factors can shape the gene pool of human populations., (Copyright © 2011 Wiley-Liss, Inc.)

Autochthonous Basques are thought to be a trace from the human population contraction that occurred during the Last Glacial Maximum, based mainly on the salient frequencies and coalescence ages registered for haplogroups V, H1, and H3 of mitochondrial DNA in current Basque populations. However, variability of the maternal lineages still remains relatively unexplored in an important fraction of the Iberian Basque community. In this study, mitochondrial DNA diversity in Navarre (North Spain) was addressed for the first time. To that end, HVS-I and HVS-II sequences from 110 individuals were examined to identify the most relevant lineages, including analysis of coding region SNPs for the refinement of haplogroup assignment. We found a prominent frequency of subhaplogroup J1c (11.8%) in Navarre, coinciding with previous studies on Basques. Subhaplogroup H2a5, a putative autochthonous Basque lineage, was also observed in Navarre, pointing to a common origin of current Basque geographical groups. In contrast to other Basque subpopulations, comparative analyses at Iberian and European scales revealed a relevant frequency of subhaplogroup H3 (10.9%) and a frequency peak for U5b (15.5%) in Navarre. Furthermore, we observed low frequencies for maternal lineages HV0 and H1 in Navarre relative to other northern Iberian populations. All these findings might be indicative of intense genetic drift episodes generated by population fragmentation in the area of the Franco-Cantabrian refuge until recent times, which could have promoted genetic microdifferentiation between the different Basque subpopulations., (Copyright © 2011 Wiley-Liss, Inc.)

Objectives: We seek to evaluate the influence of a diverse and rugged physical environment on the genetic background of human populations., Methods: We analyzed eight polymorphic Alu insertions in 226 individuals from Jujuy province (Argentina), which is composed of several regions with well-defined geographical features and marked contrasts between them associated with differences in altitude (range: 700-3300 m). This regional division was used to assess the spatial variation of the Alu diversity., Results: Deviations from Hardy-Weinberg Equilibrium expectations resulting from heterozygous deficit were found for FXIIIB and PV92 in the highest subpopulations. Several Alu elements showed genetic heterogeneity between the highest region (La Puna) and the lowest regions (Valle and Selva). Similarly, a decreasing trend of the average heterozygosity according to altitude was found. Both the centroid method and the admixture analysis unveiled a gene flow above the average in lowland populations, indicating a higher proportion of foreign genes introduced by immigrants of European and African ancestry. Furthermore, several Alu frequency clines fitting the orientation of the altitude gradient were detected., Conclusions: Our study reveals a spatial patterning of the Alu diversity in Jujuy, most likely determined by disparities in landscape and environmental features between the different subregions. Differences in the physical environment would have drastically reduced the homogenizing effects of the gene flow and would have promoted genetic drift episodes in the highest subpopulations. Microevolutionary processes detected in Jujuy have played an important role in the shaping of the gene pool of the populations from this sub-Andean zone from Argentina., (Copyright © 2010 Wiley-Liss, Inc.)

Aim: This work was intended to gain insights into the admixture processes occurring in Latin American populations by examining the genetic profiles of two ethnic groups from Antioquia (Colombia)., Subjects and Methods: To analyse the genetic variability, eight Alu insertions were typed in 64 Afro-Colombians and a reference group of 34 Hispanics (Mestizos). Admixture proportions were estimated using the Weighted Least Squares and the Gene Identity methods. The usefulness of the Alu elements as Ancestry Informative Markers (AIMs) was evaluated through differences in weighted allelic frequencies (delta values) and by hierarchical analysis of the molecular variance (AMOVA)., Results: The Afro-Colombian gene pool was largely determined by the African component (88.5-88.8%), but the most prominent feature was the null contribution of European genes. Mestizos were characterized by a major European component (60.0-63.8%) and a comparatively low proportion of Amerindian (19.2-20.7%) and African (17.0-19.3%) genes. Five of the Alu loci examined (ACE, APO, FXIIIB, PV92 and TPA25) showed an adequate resolving power to differentiate between continental groups, as indicated by delta values and AMOVA results., Conclusions: The peculiarity of the Afro-Colombian gene pool seems to be associated with intense genetic drift episodes that occurred in isolated communities founded by small groups of runaway slaves. ACE, APO, FXIIIB, PV92 and TPA25 could be efficiently utilized in studies dealing with demographic history and biogeographical ancestry in human populations.

Five short tandem repeats (STRs) located at human chromosome 6 were analysed in 97 autochthonous Basques from Guipuzcoa (northern Spain), with the aim of assessing the genetic relationships of Basques at a European scale, based on the variability of the major histocompatibility complex (MHC) region, and comparing the phylogenetic information obtained from STRs, and from HLA class I genes (HLA-A and HLA-B) for the same set of European populations. The integrative approach was focused on D6S265 and D6S2792, according to availability of population databases. F(ST) genetic distances obtained from STRs and from HLA loci were very similar, thereby describing a comparable pattern of genetic structuring among the European populations. These findings were supported by results of the Mantel test of matrix correspondence (r = 0.796, P = 0.0022) and by significant correlations between the first two F(ST) eigenvectors of STRs and HLA genes. Coinciding with previous phylogenetic studies, Basques showed substantial genetic differentiation within the European context, probably as a result of the impact of random genetic drift and high inbreeding levels for extended periods of isolation even from adjacent populations. Analysis of the geographical distribution of the allele frequencies revealed a great number of latitudinal frequency clines in both the MHC STRs and the HLA class I genes, which supports the notion of the post-glacial resettlement of Europe being a crucial factor in the genetic make-up of Europeans. Our results indicate that analysing the genetic variability of MHC microsatellites could be a suitable strategy in evaluating the role of evolutionary forces such as natural selection (because of genetic hitchhiking effect), genetic drift and gene flow in the maintenance of polymorphism at the MHC region, because STRs can efficiently complement the genetic information obtained from HLA genes.

The state of Santa Catarina (Brazil) is known to have represented a cultural crossroads in South America due to several historic migrations mainly from Europe and Africa. We set out to scrutinize whether the genetic imprint of these migrations could be traced through analysis of the matrilineal gene pool of the Catarinenses. The entire control region of the mitochondrial DNA was studied in 80 healthy and maternally unrelated individuals. The analysis of haplogroup distribution revealed that this population is extremely heterogeneous, showing the coexistence of matrilineal lineages with three different phylogeographic origins. European lineages are the most frequent due mainly to the impact of relatively recent migratory waves from Europe. In spite of this, Native American lineages and African lineages incorporated with the slave trade are also present in noticeable proportions. The strikingly high variability generated by intense gene flow is mirrored in a high sequence diversity (0.9930) and power of discrimination (0.9806). Thus, analysis of the entire mitochondrial DNA control region emerges as a valuable tool for forensic genetic purposes in this highly admixed population, an attribute common to several present-day Latin American populations.

The diffusion of the cattle pastoralism across Europe during the Neolithic period was probably accompanied by the emergence and spread of diverse contagious diseases that were unknown in the Paleolithic and that would have affected the frequency of genes directly or indirectly associated with differential susceptibility and/or resistance to infectious pathogens. We therefore propose that the high frequency of the CFTR gene, and in particular, the common Delta F508 allele mutation in current European and European-derived populations might be a consequence of the impact of selective pressures generated by the transmission of pathogenic agents from domesticated animals, mainly bovine cattle, to the man. Intestinal infectious diseases were probably a major health problem for Neolithic peoples. In such a context, a gene mutation that conferred an increased resistance to the diseases caused by pathogens transmitted by dairy cattle would have constituted a definite selective advantage, particularly in those human groups where cow's milk became an essential component of the diet. This selective advantage would be determined by an increased resistance to Cl(-)-secreting diarrheas of those individuals carrying a single copy of the Delta F508 CFTR mutation (heterozygote resistance). This hypothesis is supported by the strong association between the geography of the diffusion of cattle pastoralism (assessed indirectly by the lactase persistence distribution), the geographic distribution of a sizeable number of HLA alleles (as indicative of potential selective pressures generated by epidemic mortality) and the geographic distribution of the most common mutation causing cystic fibrosis (Delta F508). The systematic interaction of humans with infectious pathogens would have begun in northern Europe, among the carriers of the Funnel Beaker Culture, the first farmers of the North European plain, moving progressively to the south with the dissemination of the cattle pastoralism. This gradual exposure to epidemic mortality among populations located further and further south in Europe as cattle pastoralism expanded could have generated differences in CFTR gene frequencies, thereby shaping the latitudinal frequency gradients observed in present-day European populations.

We analyzed the genetic profile of 563 individuals from 12 geographically targeted human populations from Europe, Asia and Africa using 27 human-specific polymorphic Alu insertions. Phylogenetic analyses indicated a clear correspondence between genetic profiles and historical patterns of gene flow and genetic drift. Sub-Saharan African populations (Benin, Cameroon, Kenya and Rwanda) formed a visibly differentiated cluster, indicating the role of the Sahara desert as a strong natural barrier to gene flow. Moreover, a higher than expected genetic affinity between populations from Europe, North Africa and Asia was detected, probably reflecting the homogenizing effects of bidirectional migratory processes between Eurasia and North Africa during the Plio-Pleistocene and Neolithic periods or the insensitivity of these markers in discriminating between these groups. The Ami aborigines of Formosa present a distinctive degree of genetic uniqueness from all the other groups, consistent with a pattern of isolation by distance, small population size and, accordingly, substantial genetic drift. We further tested all 27 Alu loci for their potential usefulness as ancestry informative markers (AIMs). On the basis of differences between weighted allelic frequencies (delta-values) and F(ST) values, we propose that 11 of the 27 Alu elements could be useful as part of the current AIM panels to assess phylogenetic relationships.

GSTT1 and GSTM1 genes possess an inherited deletion associated with a lack of enzyme activity. The heterozygous condition of this deletion is difficult to determine in low-quality DNA with existing PCR protocols. We designed and validated a multiplex real-time PCR assay by adapting the DeltaDeltaCt relative quantification method for the analysis of GSTT1 and GSTM1 markers to accurately differentiate the three genotypes ( *1/1, *1/0, and *0/0) in degraded DNA from formalin-fixed paraffin-embedded tissue. Gene copy number values obtained provide for unambiguous homozygous and heterozygous differentiation. The efficacy shown by the PCR assay endorses its usefulness for complete genotyping of glutathione S-transferases in archival tissues.

This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish patients, whereas ACATTA-M was typical of the German cases. It is interesting to note that both haplotypes were identified in the Italian samples: GCATTA-M in a family from the Tuscany region and ACATTA-M in a family from the Veneto region. Our findings suggest the occurrence of two independent D178N-129M mutational events in Europe, preserved and transmitted from one generation to the next until nowadays. Likewise, results based on the analysis of SNP data indicate that previous hypotheses postulating that the D178N mutation had independent origins for each family and that its global distribution was determined by recurrent mutational events must be regarded with caution.

This study provides a more complete characterization of the mitochondrial genome variability of the Basques, including data on the hypervariable segment HVII of the D-loop region, which remains relatively unknown. To that end, genomic DNA from 55 healthy men living in the Arratia Valley (Biscay province) and the Goiherri region (Guipúzcoa province) was examined by direct sequencing. Three-generation pedigree charts were compiled to ensure the collection from autochthonous individuals. The most notable findings emerging from the analysis of haplogroup composition are: (i) lack of U8a mitochondrial lineage, a rare subhaplogroup recently identified in Basques and proposed as a Paleolithic marker, (ii) low frequency of haplogroup V, which conflicts with results of earlier analyses describing high frequencies in southwestern Europe, and (iii) high frequency of haplogroup J, especially subhaplogroups J1c1 and J2a. The frequency of haplogroup J does not coincide with previous mtDNA studies in present-day Basques, but is congruent with frequencies found in prehistoric and historic Basque populations. In explaining divergence in haplogroup composition between modern Basque samples, we hypothesized spatial heterogeneity promoted by population fragmentation due to extreme limitation of dispersal opportunities during the Pleistocene glaciations. Similarities between extinct and extant Basque populations as for the high frequency of lineage J, as well as the abundance of this haplogroup in northern Spain endorse a shift in the focus of attention of mtDNA analysts. A refined dissection of haplogroup J might provide more solid evidence about the process of postglacial recolonization of Europe, and thus about the shaping of the European gene pool.

The genomic diversity of the Arrernte people of Australia or caterpillar people was investigated utilizing 13 autosomal short tandem repeat (STR) markers. Significant departures from Hardy-Weinberg equilibrium were detected at the D18S51, TPOX and CSF1PO loci, which persisted after applying the Bonferroni correction. Gene diversity values oscillate between 0.6302 (CSF1PO) and 0.8731 (D21S11). Observed heterozygosity (Ho) ranges from 0.2632 (D18S51) to 0.8333 (vWA) and is lower than the expected heterozygosity (He) for 12 of the 13 loci analyzed. The genetic relationships of the Arrernte with Middle Eastern, East Asian, South Asian and Indian populations were analyzed by distance-based methods, including Neighbor-Joining trees and nonmetric multidimensional scaling. In addition, the genetic contribution of the populations included in the analysis to the Arrernte gene pool was estimated utilizing weighted least square coefficients. Although the Arrernte population exhibits a remarkable level of genetic differentiation, results of the phylogeographic analyses based on autosomal microsatellite data suggest a certain degree of genetic relatedness between the Arrernte tribe of Australia and populations from the Indian subcontinent. In contrast, the STR diversity analyses failed to detect substantial East Asian contribution to the genetic background of the Arrernte group., ((c) 2007 Wiley-Liss, Inc.)

Eight Alu sequences (ACE, TPA25, PV92, APO, FXIIIB, D1, A25 and B65) were analyzed in two samples from Navarre and Guipúzcoa provinces (Basque Country, Spain). Alu data for other European, Caucasus and North African populations were compiled from the literature for comparison purposes to assess the genetic relationships of the Basques in a broader geographic context. Results of both MDS plot and AMOVA revealed spatial heterogeneity among these three population clusters clearly defined by geography. On the contrary, no substantial genetic heterogeneity was found between the Basque samples, or between Basques and other Europeans (excluding Caucasus populations). Moreover, the genetic information obtained from Alu data conflicts with hypotheses linking the origin of Basques with populations from North Africa (Berbers) or from the Caucasus region (Georgia). In order to explain the reduced genetic heterogeneity detected by Alu insertions among Basque subpopulations, values of the Wright's F(ST )statistic were estimated for both Alu markers and a set of short tandem repeats (STRs) in terms of two geographical scales: (1) the Basque Country, (2) Europe (including Basques). In the Basque area, estimates of Wahlund's effect for both genetic markers showed no statistical difference between Basque subpopulations. However, when this analysis was performed on a European scale, F(ST) values were significantly higher for Alu insertions than for STR alleles. From these results, we suggest that the spatial heterogeneity of the Basque gene pool identified in previous polymorphism studies is relatively recent and probably caused by a differential process of genetic admixture with non-Basque neighboring populations modulated by the effect of a linguistic barrier to random mating.

This survey reports primary results of classical allele frequencies on ten protein loci in a Basque population sample from northern Navarre, the less known from an anthropological and genetic point of view than the populations of the other Basque territories of Spain. Since ancient times this has been a zone of Basque population settlement, and the Basque language (Euskera) still remains deeply rooted among its autochthonous population. A total of 122 blood samples from unrelated northern Navarrese with autochthonous ascendants to the third generation were typed for GC, HP, PI, TF, ACP1, AK1, CA2, ESD, PGD and PGM1 genetic systems. Basque surnames and birthplaces were the criteria used to define family origins. Genetic structure was analyzed on different population hierarchical levels. Northern Navarre seems to be the most genetically deviated area in comparison with other Basque groups. The highest level of differentiation is observed between Navarrese and Alava Basques whereas Guipúzcoa province, the territory adjacent to northern Navarre, presents the lowest genetic distance from the study area. Northern Navarrese show some distinguishing genetic characteristics in relation to other Basque relative samples, which include high frequencies for PI*M1 and TF*C1 and low levels of PGD*C and PGM1*2 alleles. When the genetic data reported here are analyzed jointly with GM allotypes frequencies, the results significantly reinforce the relative position of Navarrese Basques as well as the topology of the Basque cluster on genetic maps. The analysis of relationships among the genetic structures of Basque population samples leads us to ask ourselves which of them fits in best with the ancient Basque population. Classical geographers placed the tribe of the Vascones in the geographical region currently known as Navarre, so extant Navarrese Basques might be considered firm candidates to denote the anthropological and genomic distinctiveness of the ancient Basques.

Populations: Whole blood samples from 74 unrelated healthy individuals were collected. The donors' sample included Venezuelan mestizos from various regions of the country, but mostly from the resident population of Caracas City. A Venezuelan mestizo is the offspring of a mating between a native Venezuelan and a person born in Europe, mainly in Spain.

In this work, eight human-specific Alu insertion polymorphisms (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, and B65) were typed in 106 unrelated healthy individuals born in the province of Valencia (Spain), with the aim of analyzing the genetic relationships between this region of the Iberian Peninsula and other Mediterranean populations. To that end, Alu data on Eastern European, Western European, and North African populations were compiled from previous studies. The genetic information was stressed by means of genetic distances (R matrix method), nonmetric multidimensional scaling (MDS) and analyses of molecular variance (AMOVA). In Valencia, the most common Alu insertion was APO (0.940), and the least frequent was A25 (0.104). The average gene diversity (GD) computed for the sample examined was comparatively high (0.382). The insertion frequencies estimated for the eight Alu markers were very similar to the mean frequencies calculated for the whole set of populations included in the study, suggesting the hybrid nature of the Valencia's gene pool. MDS and AMOVA results generated from Alu data reveal that the Mediterranean has acted as a strong genetic boundary between the north (Europe) and the south (Northern Africa), resulting in significant gene diversity between the populations of the two regions. Restricted exclusively to the European scope, we suggest the possibility that the Mediterranean could have also acted as a migratory passageway, propitiating the dissemination of cultures and genes between the east and west of Europe and giving rise to some homogenization of gene frequencies among coastal dwelling populations., (Am. J. Hum. Biol. 18:187-195, 2006. (c) 2006 Wiley-Liss, Inc.)

In this work, we analyzed the sequence diversity of the mtDNA control region (HVI and HVII) in a sample of 48 individuals from Swanetia (Georgia), using direct fluorescent-based sequencing methods. We identified 43 different mtDNA haplotypes resulting from 78 polymorphic sites (46 in HVI and 32 in HVII). Most of the variable positions identified in both HVI and HVII were transitions (82.6 and 71.9%, respectively). The frequency of length heteroplasmy in the homopolymeric C-stretch regions was the same for both segments (10.4%). The sequence diversity increased markedly when both hypervariable regions were analyzed jointly (HVI: 0.985, HVII: 0.975, HVI+HVII: 0.994). Accordingly, the probability of two randomly selected sequences matching (random match probability, RMP) decreased from 3.4% (HVI) to 2.6% (HVI+HVII), despite which the RMP values in Georgians remained higher than estimated in most Europeans. This suggests that the variability of maternal lineages tends to be lower in traditional human isolates and, therefore, the potential of discrimination of mtDNA in forensic analysis is more limited in this type of population. The incorporation of HVII data also contributed to the refinement of results regarding the genetic relationships among the samples included in the analyses, which stress the importance of considering HVII in both population and forensic genetics.

Genomic diversity of the Qatari population was investigated by screening 15 autosomal short tandem repeats (STRs). Significant departures from genetic equilibrium were detected at the D13S317, D19S433 and VWA loci, which persisted after applying Bonferroni-type corrections. Gene diversity (GD) values ranged from 0.6851 (TPOX) to 0.8813 (D2S1338), while observed heterozygosity (Ho) oscillated between 0.3388 (D19S433) and 0.8397 (D2S1338). Interestingly, Ho was lower than expected (He) for 14 of the loci analyzed. The information provided by these microsatellite markers was analyzed by means of genetic distances, multidimensional scaling, hierarchical analyses of the molecular variance (AMOVA) and admixture estimations to assess the genetic relationships of Qatar with European, Asian, African and other Middle Eastern populations. The main findings of the study were the genetic uniqueness of the Qatari population, its strong similarity to the United Arab Emirates (UAE) group, a slight genetic differentiation with respect to other Arab populations (Syria and Egypt) and Turkey, and a certain genetic affinity with sub-Saharan African populations. These results are discussed in light of two major issues: the high consanguinity rates characterizing the Qatari population and its strategic geographic position in the Arabian Peninsula close to major migratory routes, an important pivotal contact zone for bidirectional dispersals between Eurasia and Africa., (Copyright 2006 S. Karger AG, Basel.)

The aim of this study was to investigate whether there is an increase on premature deaths due to genetically determined factors at the beginning of a demographic transition. We also analyzed the effects of parental consanguinity on offspring mortality from an epidemiological viewpoint, using parish records for family reconstitution in a Basque population (1800-1990). Among the offspring of unrelated parents, 13.1% died before their first year of life (infant mortality), and 22.8% died before the age of 16 (pre-reproductive mortality). Significant increases in both infant (23.6%) and pre-reproductive (38.5%) deaths were found among the progeny of first cousins or closer relatives, 1C (F > or = 0.0625). The corresponding relative risks of mortality were 1.79 (95% confidence limits: 1.37-2.28) and 1.68 (1.38-2.01), respectively. Estimates of the population attributable risks indicate that 4% of pre-reproductive mortality is ascribable to consanguineous unions, although kinships other than 1C produced only slight increases in offspring mortality. Evidence on the relationship between the demographic transition and the increase in premature deaths due to genetic factors was obtained through a principal component analysis (95.1% of variance accounted for). During the initial stages of the demographic transition, the population experienced substantial elevations in mean family size, natural increase of the population, frequency of close consanguineous matings (1C), and death rate due to congenital anomalies and perinatal diseases. These findings are of interest for the health services of many developing societies in Asia, Africa, and Latin America, which are nowadays immersed in the demographic transition process., (Copyright 2005 Wiley-Liss, Inc)

Allelic frequencies of 13 STR loci (D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D16S539, TH01, TPOX, CSF1PO, and D7S820) were estimated from a sample of 73 unrelated healthy donors natives of the Spanish Basque province of Vizcaya. These STR loci constitute the core of polymerase chain reaction (PCR)-based DNA genetic markers in the US Combined DNA Index System (CODIS). All STR loci analysed met Hardy-Weinberg expectations. Based upon the allelic frequencies, forensically important parameters including gene diversity (GD), polymorphism information content (PIC) and power of discrimination (PD) were calculated.

This work analyzes the spatial heterogeneity of consanguinity in the Basque province of Guipúzcoa (Spain), using data provided by Catholic dispensations (1862-1980). Secular trends in consanguinity rates (%M(C)) and mean inbreeding coefficient (F) were similar in the seven Guipúzcoan regions considered, with peaks between 1881-1920 and subsequently a gradual decline. Substantial differences in consanguinity characteristics emerged when the regions were classified according to level of urbanization. Principal component analysis (accounting for more than 85% of the total variance in consanguinity variables) clearly discriminated between urbanized and less urbanized regions. The latter stand out for their high consanguinity rates (3.57-6.73%), mean inbreeding coefficient (0.00112-0.00240), and M22/M33 ratio (M22, first cousins; M33, second cousins), which ranged between 0.89-1.48. Moreover, in less urbanized regions, marital consanguinity was eminently local, and mainly conditioned by regional endogamy (71.4-85.0%). By contrast, urban subpopulations showed the lowest consanguinity rates (1.60-1.96%) and mean inbreeding coefficient (around 0.0007). In these regions, the M22/M33 ratio also exhibited high values (1.07-1.56), but this time at the expense of the contribution of the immigrant group. Discussion of the factors that could have modeled this spatial variation in consanguinity centers on: 1) demographic aspects related to the chronology and intensity of industrialization, 2) the geography of the territory and the geography of peopling, and 3) linguistic differences, expressed in the uneven distribution of Basque-speakers among the different territories considered., (2004 Wiley-Liss, Inc.)

Genomic diversity based on 13 short tandem repeat (STR) loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX, and CSF1PO) is reported for the first time in Basques from the provinces of Guipúzcoa and Navarre (Spain). STR data from previous studies on Basques from Alava and Vizcaya provinces were also examined using hierarchal analysis of molecular variance (AMOVA) and genetic admixture estimations to ascertain whether the Basques are genetically heterogeneous. To assess the genetic position of Basques in a broader geographic context, we conducted phylogenetic analyses based on F(ST) genetic distances [neighbor-joining trees and multidimensional scaling (MDS)] using data compiled in previous publications. The genetic profile of the Basque groups revealed distinctive regional partitioning of short tandem repeat (STR) diversity. Consistent with the above, native Basques clearly segregated from other populations from Europe (including Spain), North Africa, and the Middle East. The main line of genetic discontinuity inferred from the spatial variability of the microsatellite diversity in Basques significantly overlapped the geographic distribution of the Basque language. The genetic heterogeneity among native Basque groups correlates with the peculiar geography of peopling and marital structure in rural Basque zones and with language boundaries resulting from the uneven impact of Romance languages in the different Basque territories.

In this study, allelic frequencies of the CODIS core short tandem repeat (STR) loci were estimated in a population sample consisting in 101 unrelated healthy autochthonous individuals from the Basque province of Alava (Northern Spain). Frequency distributions for all 13 STR loci were obtained using the AmpFlSTR Profiler Plus and AmpFlSTR COfiler amplification kits. The allelic frequencies generated were employed to calculate genetic and forensic useful parameters.

In this work, a sample of 116 individuals from an autochthonous Basque population (northern Navarre, Spain) was typed at the DNA level for HLA-DPA1 and HLA-DPB1 loci, with the aim of analysing the genetic polymorphism and the linkage disequilibrium (LD) of the HLA-DP region. In this Basque subpopulation, the most frequent alleles were *0103 (0.767) and *0201 (0.185) for DPA1 locus, whereas for DPB1 locus the *0401 allele was predominant (0.307). Accordingly, the most frequent haplotype was DPA1*0103-DPB1*0401 (0.300), which showed a significant LD. However, the haplotypes that most differentiated the sample of Navarre from other worldwide populations already analysed were DPA1*0105-DPB1*1901 (0.011) and DPA1*0201-DPB1*7601 (0.021), both of which showed a strong LD. Analysis of the relationships between populations based on data provided by HLA-DPA1 and HLA-DPB1 loci revealed a high genetic affinity between the Basque samples (North Navarre and Guipúzcoa), which, in turn, tend to plot separately from the remaining European populations. Gene frequency clines for DPB1*01, DPB1*04 and DPB1*11 alleles among European populations are reported for the first time. These alleles showed maximum values of F(ST) (0.033, 0.034 and 0.025, respectively). Various evolutionary forces were considered in discussing the origin of the spatial structuring of the gene frequencies: (i) gene flow, argued from the hypotheses of Post-glacial recolonization from southern Europe or the demic diffusion of farmers from the Near East into Europe, and (ii) the existence of selective pressures that could have generated genetic microdifferentiation.

Background: Somatotype, as an indirect measure of estimating body composition, provides an easy and comprehensive picture of body shape. Multiple investigations have shown the existence of an association between somatotype components and cardiovascular disease., Objective: The aim of the present study was to examine the association of somatotype with blood pressure during ageing., Methods: The Heath-Carter anthropometric somatotype and both systolic (SBP) and diastolic (DBP) blood pressures were recorded. The sample included 809 healthy institutionalized elders (370 males and 439 females) from geriatric units in Caracas, Venezuela. Ages ranged from 60 to 102 years. Product-moment correlation coefficients between somatotype components and both blood pressure readings were calculated. Principal component analysis and homogeneity analysis by means of alternative least squares tests were also performed., Results: Females were more endomorphic and mesomorphic than males. Males were more ectomorphic than females. SBP showed a downward tendency with age in males, while in females the tendency was for the SBP to increase. Correlations among variables were from low to moderate and ranged from -0.37 to +0.34 in males, and from -0.18 to +0.32 in females. Correlations tended to be stronger in the younger age group and differences between sexes were found. A negative tendency in the correlation between ectomorphy and both SBP and DBP was found, except for the oldest age group, for which the correlation was positive. Endomorphy and mesomorphy showed a stable correlation pattern with blood pressure in males, while in females this pattern was more irregular and less consistent., Conclusion: Individuals with high levels of SBP and DBP had mean somatotypes, which were similar to those of other male groups characterized by myocardial infarct, coronary heart disease and the risk of hypertension, indicating that these somatotypes may be associated with cardiovascular risk factors. In particular, our results indicate that individuals who present a cardiovascular risk profile are more endomorphic and mesomorphic and less ectomorphic than those with a lower cardiovascular risk profile., (Copyright 2004 S. Karger AG, Basel)

Analysis of the interaction between mortality patterns and opportunity for natural selection could help to elucidate potential evolutionary implications of epidemic mortality. In this paper secular trends are studied in relation to Crow's index (It) and its components of mortality (Im) and fertility (If), using parish records for family reconstitution in a Basque population. A principal components analysis (91% of the variance accounted for) showed marked quantitative and qualitative variations of Im and If depending on the stage of demographic transition of the population analyzed: In pretransitional societies the opportunity for natural selection is determined mainly by differential prereproductive mortality, whereas in posttransitional societies selection resulting from differential fertility plays a key role. The highest values for the mortality component (range 0.81-1.26) and for the relative contribution of Im, to It (range 47.1-57.2%) were observed in periods with a high incidence of infectious diseases and when the most severe mortality crises were detected (1830-1859, 1860-1889, and 1890-1919). A differential incidence of epidemic mortality was also found at prereproductive ages (before 16 years) and at reproductive ages (16-45 years), which provides strong support for the idea of the long-term genetic consequences of mortality crises.

Celiac disease (CD) is a complex and multifactorial disease, defined as a malabsorptive disorder of the small intestine resulting from ingestion of gluten. Genetic susceptibility to CD has been associated with human leukocyte antigen (HLA)-DQ2 heterodimer, encoded by the DQA1*0501 and DQB1*02 genes. However, HLA risk factors do not explain the whole genetic predisposition: not all DQ2-encoding haplotypes confer equal susceptibility to CD. The aim of the present work was to confirm the aforementioned findings in a southern European population. With this purpose, 136 unrelated children diagnosed with CD were typed at the DNA level for HLA-DQA1 and -DQB1 loci. Patients are currently attended at the Donostia Hospital (province of Guipúzcoa, Spain). HLA class II typing was performed by polymerase chain reaction-sequence specific primer procedures. Conspicuous frequencies of the alleles associated with susceptibility to CD were observed (DQA1*0501: 0.592, DQB1*0201: 0.471). Accordingly, the haplotypes DQA1*0501-DQB1*0201 and DQA1*0201-DQB1*0202 revealed a strong linkage disequilibrium (18.84% and 18.75%, respectively) when compared with the Spanish general population. Of the total sample, 93.4% (127 individuals) were carriers of DQ2 heterodimer, either in homozygosis or in heterozygosis. This percentage coincides with figures reported in previous studies, implying the effect of other genes in the development of CD.

The focus of this work is the analysis of changes in completed family size and possible determinants of that size over time, in an attempt to characterize the evolution of reproductive patterns during the demographic transition. With this purpose in mind, time trends are studied in relation to the mean number of live births per family (as an indirect measure of fertility), using family reconstitution techniques to trace the reproductive history of each married woman. The population surveyed is a Spanish rural community called Lanciego, located at the southern end of the province of Alava (Basque Country). A total of 24,510 parish records of baptisms, marriages and burials made between 1800 and 1969 were examined to obtain the demographic data set. For each reconstituted family, the variables included in the study were the number of live births per family or family size (FAMS), year of marriage (YEAR), age at marriage of both partners (AMAN, AWOM), wife's age at the end of marriage (WEND), duration of marriage (MARD), age at first maternity (A1CH), length of reproductive span (REPS) and number of children dying before their first anniversary (MINF). Through a principal component analysis, three factors were found that explained more than 75% of the total variance. Association of variables in factors I and III was particularly useful in characterizing the variability of mean family size in pre-transitional, transitional and post-transitional cohorts. During demographic transition, a decreasing trend is observed in the variables FAMS, REPS and MINF, while variables AWOM, AMAN, WEND and A1CH show a tendency to increase over the 20th century. Results obtained by multiple regression analysis confirm that the best predictors of family size (dependent variable) were REPS and MINF, which between them explained over 85% of the total variation in FAMS (R2 = 0.853). In Lanciego, birth control seems to be present on the evidence of an increase in age at first maternity and a decrease in age at last parturition, indicating that the beginning of the reproductive span is delayed and its end is brought forward. Interaction between family size and infant mortality is discussed in the light of various hypotheses, including replacement of descendants, the so-called biological effect and the theory of r and k selection.

In this work, a sample of 112 individuals from an autochthonous Basque population (Northern Navarre, Spain) were typed at the DNA level for the HLA-DQA1 locus, with the aim of characterizing its polymorphism and analyzing the genetic relationships of Basque Navarrese with other Caucasian populations. Northern Navarre is a neighboring area with Guipúzcoa, a province located in the core of the Basque territory having the highest proportion of Basque-speakers. In Navarrese population, the most frequent alleles were DQA1*01 (0.375) and DQA1*02 (0.259). Frequency clines for both DQA1*0103 allele and DQA1*04* allele cluster (including DQA1*0401, DQA1*0501 and DQA1*0601) among the European and Mediterranean populations considered are reported for the first time. Furthermore, a spatial structuring previously described for DQA1*02 allele is corroborated. The information provided by the highly polymorphic HLA-DQA1 locus was stressed by using genetic distances and non-metrical multidimensional scaling (MDS). The analysis of genetic relationships among populations showed a high genetic affinity between the Basque subpopulations of Northern Navarre and Guipúzcoa, which in turn tended to plot separately from the remaining European and Mediterranean populations. In the same way, the Basques showed no clear relationship to North African populations, as postulated in several previous HLA studies. The observed genetic heterogeneity seems to be conditioned by the high frequencies of the DQA1*02 allele in Basques from Guipúzcoa and North Navarre. These two subpopulations seem to show low levels of admixture with other non-Basque neighboring populations, probably because of their deeply rooted ethnicity and the existence of a linguistic barrier to random mating.

Inbreeding in the Orozco Valley (Basque Country, Spain) between the 18th and 20th centuries was investigated on the basis of ecclesiastical dispensations and surname lists. The variations over time are very similar to those observed elsewhere in Europe, with a major increase in the coefficient of inbreeding in the late 19th and early 20th centuries. This is due mainly to an increase in marriages between first cousins. A highly marked decrease in inbreeding is observed during the 20th century. The secular trends described by the coefficient calculated on the basis of dispensations and by that calculated on isonymy are very similar. The nonrandom component of isonymy reveals a selective search for a related spouse during the period of maximum inbreeding. These results are associated with the process of demographic transition which affected European populations as a whole in the 19th century, resulting in a greater availability of kin among potential mates and thus enabling inbreeding to increase to levels far higher than those observed for earlier centuries., (Copyright 2002 Wiley-Liss, Inc.)

In this work, the evolution of demographic and health patterns in a Basque rural population from Spain is analysed, as they relate to progress in demographic and epidemiological transition. For this purpose, parochial record data on 13,298 births and 9,215 deaths, registered during the 19th and 20th centuries (1800-1990), were examined. The study area is a rural community called Lanciego, which is located at the southern end of the Rioja Alavesa area (Alava Province, Basque Country). In Lanciego, demographic transition began in the final decade of the 19th century, when a definite, irreversible trend began towards a reduction in mortality. The decrease in the birth rate came later than that in the death rate, and did not start until the 1930s. The post-transitional stage seemed to be reached in the 1970s, when the birth and death rates showed values below 20 per 1,000. Other characteristics observed for the post-transitional stage in Lanciego are: (i) very low rates of infant mortality achieved at the expense of effective control of exogenous mortality; (ii) the mortality curve by ages changes from a U-shape (typical of populations with a high infant mortality rate and low life expectancy at birth) to a J-shape more characteristic of modern societies where longevity and life expectancy are considerably higher; (iii) a certain level of over-mortality among women in the senior age group (>65); and (iv) a significant proportion of mortality in recent times (1970-90) resulting from cardiovascular diseases and malignant neoplasms (post-transition causes). This last point is in contrast with observations from the first four decades of the 20th century, when infectious diseases and respiratory ailments were determining factors in mortality among this population. The data provided by the study of the variation over time in demographic and health patterns indicate that reducing the risk of mortality is one of the most important preconditions for fertility decline.