Piero Santolamazza

A Back Migration from Asia to Sub-Saharan Africa Is Supported by High-Resolution Analysis of Human Y-Chromosome Haplotypes

The variation of 77 biallelic sites located in the nonrecombining portion of the Y chromosome was examined in 608 male subjects from 22 African populations. This survey revealed a total of 37 binary haplotypes, which were combined with microsatellite polymorphism data to evaluate internal diversities and to estimate coalescence ages of the binary haplotypes. The majority of binary haplotypes showed a nonuniform distribution across the continent. Analysis of molecular variance detected a high level of interpopulation diversity (PhiST=0.342), which appears to be partially related to the geography (PhiCT=0.230). In sub-Saharan Africa, the recent spread of a set of haplotypes partially erased pre-existing diversity, but a high level of population (PhiST=0.332) and geographic (PhiCT=0.179) structuring persists. Correspondence analysis shows that three main clusters of populations can be identified: northern, eastern, and sub-Saharan Africans. Among the latter, the Khoisan, the Pygmies, and the northern Cameroonians are clearly distinct from a tight cluster formed by the Niger-Congo-speaking populations from western, central western, and southern Africa. Phylogeographic analyses suggest that a large component of the present Khoisan gene pool is eastern African in origin and that Asia was the source of a back migration to sub-Saharan Africa. Haplogroup IX Y chromosomes appear to have been involved in such a migration, the traces of which can now be observed mostly in northern Cameroon.

Phylogeographic analysis of haplogroup E3b (E-M215) y chromosomes reveals multiple migratory events within and out of Africa.

We explored the phylogeography of human Y-chromosomal haplogroup E3b by analyzing 3401 individuals from five continents. Our data refine the phylogeny of the entire haplogroup, which appears as a collection of lineages with very different evolutionary histories, and reveal signatures of several distinct processes of migrations and/or recurrent gene flow that occurred in Africa and western Eurasia over the past 25000 years. In Europe, the overall frequency pattern of haplogroup E-M78 does not support the hypothesis of a uniform spread of people from a single parental Near Eastern population. The distribution of E-M81 chromosomes in Africa closely matches the present area of distribution of Berber-speaking populations on the continent, suggesting a close haplogroup-ethnic group parallelism. E-M34 chromosomes were more likely introduced in Ethiopia from the Near East. In conclusion, the present study shows that earlier work based on fewer Y-chromosome markers led to rather simple historical interpretations and highlights the fact that many population-genetic analyses are not robust to a poorly resolved phylogeny.

Human Y-chromosome variation in the western mediterranean area: Implications for the peopling of the region

Y-chromosome variation was analyzed in a sample of 1127 males from the Western Mediterranean area by surveying 16 biallelic and 4 multiallelic sites. Some populations from Northeastern Europe and the Middle East were also studied for comparison. All Y-chromosome haplotypes were included in a parsimonious genealogic tree consisting of 17 haplogroups, several of which displayed distinct geographic specificities. One of the haplogroups, HG9.2, has some features that are compatible with a spread into Europe from the Near East during the Neolithic period. However, the current distribution of this haplogroup would suggest that the Neolithic gene pool had a major impact in the eastern and central part of the Mediterranean basin, but very limited consequences in Iberia and Northwestern Europe. Two other haplogroups, HG25.2 and HG2.2, were found to have much more restricted geographic distributions. The first most likely originated in the Berbers within the last few thousand years, and allows the detection of gene flow to Iberia and Southern Europe. The latter haplogroup is common only in Sardinia, which confirms the genetic peculiarity and isolation of the Sardinians. Overall, this study demonstrates that the dissection of Y-chromosome variation into haplogroups with a more restricted geographic distribution can reveal important differences even between populations that live at short distances, and provides new clues to their past interactions.

Differential structuring of human populations for homologous X and Y microsatellite loci.

The global pattern of variation at the homologous microsatellite loci DYS413 (Yq11) and DXS8174 and DXS8175 (Xp22) was analyzed by examination of 30 world populations from four continents, accounting for more than 1,100 chromosomes per locus. The data showed discordant patterns of among- and within-population gene diversity for the Y-linked and the X-linked microsatellites. For the Y-linked polymorphism, all groups of populations displayed high FST values (the correlation between random haplotypes within subpopulations, relative to haplotypes of the total population) and showed a general trend for the haplotypes to cluster in a population-specific way. This was especially true for sub-Saharan African populations. The data also indicated that a large fraction of the variation among populations was due to the accumulation of new variants associated with the radiation process. Europeans exhibited the highest level of within-population haplotype diversity, whereas sub-Saharan Africans showed the lowest. In contrast, data for the two X-linked polymorphisms were concordant in showing lower FST values, as compared with those for DYS413, but higher within-population variances, for African versus non-African populations. Whereas the results for the X-linked loci agreed with a model of greater antiquity for the African populations, those for DYS413 showed a confounding pattern that is apparently at odds with such a model. Possible factors involved in this differential structuring for homologous X and Y microsatellite polymorphisms are discussed.

Realidad social de los pacientes con isquemia crítica de miembros inferiores

Realidad social de los pacientes con isquemia critica de miembros inferiores Resumen. Objetivo. Realizar una aproximacion a la realidad social de los pacientes que alcanzan los estadios mas avanzados de isquemia cronica de miembros inferiores (MMII) (isquemia critica). Pacientes y metodos. Se registran mediante entrevista a paciente y familiar, datos relacionados con la vivienda habitual, entorno sociofamiliar, recursos economicos y nivel de instruccion de 50 pacientes ingresados en nuestro servicio con el diagnostico de isquemia critica de MMII, entre el 1 de octubre y el 31 de diciembre de 2005. Se realiza una comparacion posterior con los mismos datos de la Encuesta de condiciones de vida del Instituto Nacional de Estadistica (INE) correspondiente a la zona estudiada y al mismo grupo de edad. Resultados. La media de edad de los pacientes es de 69,1 anos, siendo el 84% hombres y el 16% mujeres. Se constata una tasa de pobreza relativa del 50% en los pacientes con isquemia critica frente al 24,8% en la poblacion local correspondiente a la edad. El 26% de los pacientes estudiados son analfabetos, frente al 11,5% de la poblacion general. Con respecto a la vivienda, el 32% de los pacientes viven en un piso alto sin ascensor, y este porcentaje se mantiene en pacientes a los que se les somete a una amputacion mayor. Conclusiones. Constatamos una tendencia a la exclusion social en los pacientes con isquemia grave de las extremidades. Dicha realidad social debe ser conocida por el cirujano vascular a la hora de tratar a estos pacientes, imponiendose un abordaje multidisciplinar junto con trabajadores sociales, medicos de familia y personal de enfermeria y asistencia domiciliaria. [ANGIOLOGIA 2008; 60: 241–5]

Patterns of male‐specific inter‐population divergence in Europe, West Asia and North Africa

We typed 1801 males from 55 locations for the Y‐specific binary markers YAP, DYZ3, SRY10831 and the (CA)n microsatellites YCAII and DYS413. Phylogenetic relationships of chromosomes with the same binary haplotype were condensed in seven large one‐step networks, which accounted for 95% of all chromosomes. Their coalescence ages were estimated based on microsatellite diversity. The three largest and oldest networks undergo sharp frequency changes in three areas. The more recent network 3.1A clearly discriminates between Western and Eastern European populations. Pairwise Fst showed an overall increment with increasing geographic distance but with a slope greatly reduced when compared to previous reports. By sectioning the entire data set according to geographic and linguistic criteria, we found higher Fst‐on‐distance slopes within Europe than in West Asia or across the two continents.

Characterization of a Small Family (CAIII) of Microsatellite-Containing Sequences with X-Y Homology

Abstract. Four X-linked loci showing homology with a previously described Y-linked polymorphic locus (DYS413) were identified and characterized. By fluorescent in situ hybridization (FISH), somatic cell hybrids, and YAC screening, the X-linked members of this small family of sequences (CAIII) all map in Xp22, while the Y members map in Yq11. These loci contribute to the overall similarity of the two genomic regions. All of the CAIII loci contain an internal microsatellite of the (CA)n type. The microsatellites display extensive length polymorphism in two of the X-linked members as well as in the Y members. In addition, common sequence variants are found in the portions flanking the microsatellites in two of the X-linked members. Our results indicate that, during the evolution of this family, length variation on the Y chromosome was accumulated at a rate not slower than that on the X chromosome. Finally, these sequences represent a model system with which to analyze human populations for similar X- and Y-linked polymorphisms.

Linkage disequilibrium analysis of the human adenosine deaminase (ada) gene provides evidence for a lack of correlation between hot spots of equal and unequal homologous recombination.

The linkage disequilibrium (LD) pattern within the adenosine deaminase (ADA) gene was analyzed by studying 13 polymorphic loci in 137 families from two European and three African populations. Evidence for the presence of a 12-kb meiotic crossover hot spot, spanning part of the first and the second intron and flanked by regions of reduced recombination activity, was obtained. Moreover, segregation analysis of 113 informative meioses revealed two recombination events that are internal or overlap the 12-kb region, thus suggesting a recombination rate for the hot-spot region about 50-fold higher than the mean rate across the human genome. Within the hot spot, a 144-bp palindromic sequence was also identified and its possible involvement in the recombination process is discussed. The 12-kb region characterized by the low degree of LD does not include the 3.2-kb region that is deleted, as a result of recurrent unequal homologous recombination between two Alu elements, in patients affected by autosomal severe combined immunodeficiency. This observation provides the first evidence for an absence of correlation between hot spots of equal and unequal homologous recombination.

An MspI polymorphism in the X-specific region proximal to the pseudoautosomal boundary. A new example of a unique “African” marker?

A polymorphic MspI site was located in the X-specific region proximal to the pseudoautosomal boundary. Two alleles defined by the absence or the presence of the MspI site were detected by the polymerase chain reaction (PCR) in a sample of Bantu-speaking individuals from Cameroon. No variation for this site was observed in a population sample from Italy.