Ana M. Pérez-Miranda

Qatari DNA Variation at a Crossroad of Human Migrations

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.

Microsatellite data support subpopulation structuring among Basques.

AbstractGenomic 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 FST 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.

The maternal legacy of Basques in northern navarre: New insights into the mitochondrial DNA diversity of the Franco-Cantabrian area.

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.

Polymorphic Alu insertions and the genetic structure of Iberian Basques

AbstractEight 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 Wrights FST 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 Wahlunds effect for both genetic markers showed no statistical difference between Basque subpopulations. However, when this analysis was performed on a European scale, FST 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.

An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European 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 cows 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.

Autosomal STR variation in five Austronesian Populations

Abstract Human population characteristics at the genetic level are integral to both forensic biology and population genetics. This study evaluates biparental microsatellite markers in five Austronesian-speaking groups to characterize their intra- and interpopulation differences. Genetic diversity was analyzed using 15 short tandem repeat (STR) loci from 338 unrelated individuals from 5 Pacific islands populations, including the aboriginal Ami and Atayal groups from Taiwan, Bali and Java in Indonesia, and the Polynesian islands of Samoa. Allele frequencies from the STR profiles were determined and compared to other geographically targeted worldwide populations procured from recent literature. Hierarchical AMOVA analysis revealed a large number of loci that exhibit significant correspondence to linguistic partitioning among groups of populations. A pronounced divide exists between Samoa and the East (Formosa) and Southeast Asian (Bali and Java) islands. This is clearly illustrated in the topology of the neighbor-joining tree. Phylogenetic analyses also indicate clear distinctions between the Ami and Atayal and between Java and Bali, which belie the respective geographic proximities of the populations in each set. This differentiation is supported by the higher interpopulation variance components of the Austronesian populations compared to other Asian non-Austronesian groups. Our phylogenetic data indicate that, despite their linguistic commonalities, these five groups are genetically distinct. This degree of genetic differentiation justifies the creation of population-specific databases for human identification.

Microsatellite DNA markers from HLA region (D6S105, D6S265 and TNFa) in autochthonous Basques from Northern Navarre (Spain).

Background : The extent of the genetic polymorphism of the HLA complex is becoming well characterized in Basque population and their subpopulations. This level of knowledge mainly concerns HLA class I loci. However, Basque population surveys dealing with HLA class II genes and/or microsatellites in the HLA region are still very scarce. Aim : The population genetics of three highly polymorphic short tandem repeat (STR) loci, D6S105, D6S265 and TNFa, from HLA region has been analysed in autochthonous (indigenous) Basques from Northern Navarre (Spain). The same blood samples have been typed for HLA class II genes from DQ/DR/DP regions and some findings from that information can be found therein. Subjects and methods : Blood samples were taken from 107 unrelated autochthonous Basques from Northern Navarre. The criterion used to define Northern Navarrese identity was that of three generations of Basque surnames and birthplaces. Results : The main features observed in Navarrese Basques were the rather high frequencies of alleles D6S105*4 and D6S265*7. A novel allele has been detected at the D6S265 locus (13: 145 bp). The most frequent haplotype was D6S105*8-D6S265*4 with a highly significant linkage disequilibrium being presented. The high frequency of allele TNFa*1 in Basques is noteworthy and this characteristic is not shared by other European populations, where TNFa*1 is absent or shows negligible values. The multidimensional scaling analysis (MDS) for TNFa allele frequencies has shown a high variability among populations and that alleles TNFa*1 ( F ST = 0.0615) and TNFa*12 ( F ST = 0.0424) seem to have significant influence over the spatial population configuration. TNFa*2 showed the lowest FST value (0.0077) because of its conspicuous homogeneous distribution all over the European populations. Conclusions : Findings shown here on HLA microsatellites and their relationships with other HLA class I and class II genes in Basques can be helpful for those studies mainly addressed at detecting associations between HLA genes and diseases in the Basque area as a whole, and particularly in its autochthonous population, settled there since remote times.

Allele Variation of DYS19 and Y- Alu Insertion (YAP) Polymorphisms in Basques: An Insight into the Peopling of Europe and the Mediterranean Region

Two Y-chromosome DNA polymorphisms, the DYS19 microsatellite and the YAP (at locus DYS287), were tested in males from two autochthonous Basque populations from France and northern Navarre (Spain). The results are compared to those obtained for the same genetic markers in 32 populations from Europe, northern Africa, and western Asia. The high predominance of the DYS19*11 (190-base-pair) allele in Basques indicates that their genetic diversity for microsatellite DYS19 is around half that observed in Europeans, North Africans, and western Asians. The Y-Alu insertion (YAP+) was not detected in the Basque samples. This study attempts to throw some light on the importance of historically recent migratory movements, the main corridors of gene flow, and demographic sizes and their variations in shaping gene frequency patterns in contemporary human populations, particularly in the Mediterranean region. Historical processes may have had more significant effects on the genetic make-up of current human populations than those of prehistoric times.

Genetic admixture estimates by Alu elements in Afro-Colombian and Mestizo populations from Antioquia, Colombia

Abstract 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 (δ 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 δ 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.

Microsatellites and Alu elements from the human MHC in Valencia (Spain): analysis of genetic relationships and linkage disequilibrium.

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.