Cultural transmission of fertility has been described in several human populations. Using the example of the French Canadian population of Charlevoix-Saguenay Lac-saint Jean, we show by a simulation study that this process enables initially very rare disease alleles to reach extremely high frequencies in the population. We also show that it increases the allelic association between the disease locus and closely linked marker loci, and thus affects any linkage disequilibrium mapping. Finally we develop methods to detect this fertility transmission and estimate its intensity in populations. The first method consists in using the frequency of rare disease alleles and their level of allelic association with nearby markers to estimate the growth rate of the population. If this estimated growth rate is much above the known demographic growth rate, this is a clear indication of an underlying demographic process, such as fertility transmission. We also show that fertility transmission affects also the shape of the coalescent tree of each gene in the population, and that it could be used to develop a more accurate estimate of the level of fertility transmission. In conclusion such a cultural transmission can have a strong impact on the evolution of Human gene pool and could partly explain the low effective population size of our species.

Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of Fst.  Low outliers relative to an appropriate neutral population-genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection.  However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of Fst estimates, and current methods have not yet been tested in large-scale simulation experiments.  We simulate data from a structured population at many neutral loci, interspersed with loci subject to adaptive or balancing selection, and use it to examine the performance of FDIST, the frequentist method of Beaumont & Nicols (1996) that employs moment-based estimates of Fst, in distinguishing the loci simulated under selection from the neutral loci.  We also describe and compare the performance of a novel hierarchical-Bayesian method, based on the multinomial-Drichlet likelihood and implemented via Markov chain Monte Carlo. This is joint work with Mark Beaumont, University of Reading UK.

The extent to which natural selection shapes diversity within populations is a key question for population genetics. Thus, there is considerable interest in quantifying the strength of selection. A full likelihood approach for inference about the selection coefficient of a single selected site within an otherwise neutral fully linked sequence in a coalescent setting is described in this talk. The full information is used in this approach and hence it is often preferable to summary statistics. It has the following desirable qualities. It allows for the possibility of the hypothesis of selection to be tested in a likelihood ratio setting. The likelihood surface of the selection coefficient is also obtainable allowing the MLE to be found, and the distribution of ages of the mutations and clades under mutations is also calculable. The approach is general and can be used for any di-allelic selection scheme. Selection is incorporated through modelling the frequency of the allelic classes stochastically back through time and then using a subdivided coalescent recursion. An importance sampling algorithm is then used to explore over coalescent tree space consistent with the data, under the infinite sites assumption.

It has been long recognized that population demographic expansions lead to distinctive features in the molecular diversity of populations. However, recent simulation results suggested that a distinction could be made between a pure demographic expansion in an unsubdivided population, and a range expansion in a subdivided population, both leading to a large increase in the total number of the individuals. In order to better characterize the effect of a range expansion, we derive the distribution of the number of mutation differences between pairs of genes (the mismatch distribution), the heterozygosity, the average number of pairwise difference, and the fixation index FST after an instantaneous range expansion in an infinite-island model. These derivations are shown by simulation to lead to results qualitatively similar to those one would obtain after a range expansion in a 2-dimensional stepping-stone model. How these results can be used to estimate the parameters of the range expansion (timing, size increase, immigration rate) is discussed. An importance-sampling procedure for estimating underlying range expansion parameters is also introduced.

Inference of demographic parameters from genetic data under isolation by distance models can be done using summary statistic (e.g. F-statistics) methods or using maximum likelihood methods. In the first part of my talk, I will present some results on the robustness to sampling, mutational, and historical factors of a given method of estimation based on F-statistics. This method is based on the regression of Fst-like estimates against the geographical distance between populations (or individuals for continuous populations) and seems very robust to most of the factors tested. In a second part, I will present some results on the estimation of demographic parameters with maximum likelihood methods. Those results, based on real and simulated data sets, show that maximum likelihood methods are at their beginning and that, at this stage, using them to estimate demographic parameters is risky. The Fst-based method seems thus to be more precise and robust at the moment than maximum likelihood methods to infer demographic parameters from genetic data under isolation by distance.

Understanding the processes and patterns of gene flows and local adaptation requires a detailed knowledge of how landscape characteristics structure populations. Geographically explicit analysis of genetic variation (“landscape genetics”), will help our understandings. In this talk, after presenting the recent developments of molecular tools, we will discuss the use and limits of some statistical tools that can be used to analyse the genetic variation in relation to geography.  We will focus on those tools which require innovative sampling schemes and sampling populations which are uniformly distributed across the landscape.
 
 

Related articles:
Manel S., Schwartz M.K., Luikart G. and Taberlet P. (2003) Landscape genetics: combining landscape ecology and population genetics. Trends in Ecology and Evolution, 18: 189-97.

 

When sampling locations are known, the association between genetic and geographic distances can be tested by spatial autocorrelation or regression methods. These tests give some clues to the possible shape of the genetic landscape. Nevertheless, correlation analyses fail when attempting to identify where genetic barriers may exist, namely the areas where a given variable shows an abrupt rate of change. To this end, a computational geometry approach is more suitable since it provides the locations and the directions of barriers and it can show where geographic patterns of two or more variables are similar. In this frame we have implemented the Monmonier’s (1973) maximum difference algorithm in a new software in order to identify genetic barriers. 
To provide a more realistic representation of the barriers in a genetic landscape, a significance test was implemented in the software by means of bootstrap matrices analysis. As a result, i) the noise associated in genetic markers can be visualized on a geographic map and ii) the areas, where genetic barriers are more robust, can be identified. Moreover, this multiple matrices approach can visualize iii) the patterns of variation associated to different markers in a same overall picture. 
This improved Monmonier’s method is highly reliable since, to identify genetic structures, it doesn’t interpolate original data as the Womble method (1951) and the geographic plot of principal components do. Moreover, it can be applied to a wider range of data than genetic: whenever sampling locations and a distance matrix between corresponding data are available.
 
 

Related articles:
Manni F., Guèrard E. & Heyer E. (2004) Geographic patterns of variation (genetic, morphologic, linguistic, etc.): how barriers can be detected by “Monmonier’s algorithm”. Human Biology, (accepted).

Although many studies have reported human polymorphism data, there has been no analysis of the effect of sampling design on the patterns of variability recoverd.  Here, we consider which factors affect a summary of the allele frequency spectrum.  The most important variable to emerge from our analysis is the numbr of ethnicities sampled: studies that sequence individuals from more ethnicities recover more rare alleles.
These observations are consistent with fine-scale geographic differentiation as well as population growth.  They suggest that the geographic sampling strategy should be considered carefully, especially when the aim is to infer the demographic history of humans.
 
 

Related articles:
Ptak S.E. & Przeworski M. (2002) Evidence for population growth in humans is confounded by fine-scale population structure. Trends Genet.18: 559-63.
Hammer M.F., Blackmer F., Garrigan D., Nachman M.W., Wilder JA. (2003) Human population structure and its effects on sampling Y chromosome sequence variation. Genetics164:1495-509.

Understanding the interaction of selection and recombination is essential for interpreting patterns of linkage disequilibrium in natural populations. Under a neutral model of evolution the rate of recombination relative to genetic drift predicts both the number of distinct ancestries underlying a region of a genome, and the correlation between them. For this reason an estimate of the population scaled rate of recombination is important in many areas of genetics, from understanding pathogen evolution to mapping disease loci.
When recombination rates cannot be estimated directly (e.g. using pedigree based methods or sperm typing) it is possible to infer the underlying rate of recombination from the genetic diversity apparent in random samples of unrelated individuals. A number of parametric methods (using a range of approaches; full-likelihood, summary/composite likelihood and moment estimation) have been suggest for inferring recombination rates, each relying on the key assumption of selective neutrality. 
By simulating from a coalescent model with recombination and caricatures of natural selection we investigate the effects of violating the neutral model on recombination rate estimates. The results are interpreted by considering the distortion to underlying genealogies and the correlations between them. With the inclusion of mutations this is equivalent to considering the frequency distribution of segregating sites and the structure of linkage disequilibrium.  Conclusions are particularly relevant to those interested in detecting natural selection in recombining genomes and/or interpreting empirical patterns of linkage disequilibrium.

Single Nucleotide Polymorphisms (SNPs) with a documented role in modulating pathogen response are likely to have been under selection constraints. It is unclear whether such selection constraints will result in greater genetic stratification for such SNPs compared to other SNPs.  Using a population of 1600 Irish patients of Acute Coronary syndromes for which the geographic origin (32 Irish counties) was known for all four grandparents, we aimed to determine if there was greater geographic stratification of pathogen response-related SNPs.  This population was genotyped for 26 SNPs in total.  15 of which are involved in the modulation of the response to certain pathogens, and 11 which have been shown to modulate platelet function in cardiovascular disease. We wished to determine if the pathogen response SNPs showed a more marked geographic differentiation than the platelet SNPs in Ireland in relation to possible selection pressure.
1-D spatial autocorrelation analysis using the allele frequencies for each of the Irish counties showed that there is little genetic structure in this population (Moran’s I statistic, p>0.05). 2-D spatial autocorrelation analysis of all SNPs provides suggestive evidence to support this. However for the pathogen response SNPs, there was a significant north-south gradient (Moran’s I, p<0.05) contributed to mainly by one SNP, the VDR FokI variant (p=0.005). The other SNPs showed no significant gradient. 
In conclusion, population structure is unlikely to heavily bias case-control studies in small defined Caucasian populations such as the Irish, but correction for structure may be more important for genes under possible selection pressures.

The amount and geographic patterning of human genetic variation is an evolutionary consequence of several historical and contemporary processes including population expansion, demographic subdivision, and migration.  Quantifying this variation, and in turn the extent to which these forces have acted in shaping human genetic structure is a key component to understanding the evolution of human populations.  Here we present an analysis framework based upon graph-theory, which we call Population Graphs (PG).  While the PG framework allows the extraction of traditional population genetic statistics such as differentiation (FST) and isolation by distance (Mhat), topological analysis of the connectedness among human populations provides heretofore-unattainable information on intra-population evolutionary history.  We highlight the utility of the PG framework using data consisting of 1056 individuals assayed for 376 variable microsatellite loci sampled from 52 populations around the globe.  An analysis of the topology of the human graphs using graph-theoretic algorithms reveals the following characteristics of human population genetic structure.  First, groups of populations exhibit significant topological structuring consistent with geographically relevant population subdivisions.  Second, the topological distances among populations are significantly correlated with geographic separation supporting the notion of isolation by distance and spatially proximate migration patterns.  Finally, we show how the topology of the graph is used to identify specific populations whose patterns of connectivity prove to be critical to the movement of genetic information across the entire graph.  We close by discussing sampling specifics and extensions of the PG framework for further understanding the evolution of human genetic structure.

Understanding the evolutionary consequences of different classes of amino acid mutations in the human genome is of great medical and evolutionary interest. Comparing levels of genetic variation within the human genome to levels of divergence between the human and chimpanzee genomes across different classes of sites is a powerful technique for addressing this problem. Here, we analyze 8,166 variable nucleotide sites located in coding and non-coding regions for 291 autosomal genes as discovered by direct sequencing of a panel of ethnically diverse humans (n = 158 chromosomes) and a male Western chimpanzee (Pan troglodytes). We find strong evidence that different classes of amino acid replacement mutations, defined by various physical and chemical considerations, are subject to different intensities of weak negative selection. We demonstrate a greater than two fold difference in the rates of evolution of non-lethal amino acid mutations, with physicochemically radical mutations evolving, on average, at roughly 32% the rate of synonymous and non-coding mutations and physicochemically conservative amino acid mutations, on average, evolving at 65\% the rate of synonymous and non-coding mutations. We also demonstrate considerable variation in the strength of selection within each of these classes, and provide evidence for weak negative selection operating on roughly half of all amino acid mutation classes. Lastly, we demonstrate that mutations at certain CpG codons are significantly weakly deleterious, yet occur at above the neutral mutation rate, suggesting that the CpG mutation bias has a significant fitness consequence in human populations.

As human populations dispersed throughout the world, they were subject to new environments, diets, parasites, and diseases, which must have led to local adaptation via natural selection and hence altered patterns of genetic variation.   Yet there are very few examples known where such local selection has clearly influenced human genetic variation.  The usual way to try to identify local selection acting on human genes has been the "candidate gene" approach, in which particular genes are investigated that are suspected to influence a particular trait thought to be under selection. An alternative approach is to screen random loci across the genome; those loci that exhibit unusually large genetic distances between human populations are then potential markers of genomic regions under local selection. 
We investigated this approach by genotyping 332 short tandem repeat (STR) loci in Africans and Europeans and calculating the genetic differentiation for each locus (Kayser et al., MBE 20:893-900, 2003).  Patterns of genetic diversity at these loci were consistent with greater variation in Africa, and with local selection operating on populations as they moved out of Africa.  For 11 loci exhibiting large genetic distance values, we identified and genotyped a nearby STR locus located within 20 kb of the original target STR locus.  The genetic distances for these nearby loci were significantly larger than average, indicating that the genomic regions containing the target and nearby STR loci reproducibly exhibit larger genetic distances between populations than the "average" genomic region.
Genes within these genomic regions that exhibit large genetic distance values are candidates for local selection.  We are currently investigating several such candidates by a combination of sequencing and SNP-genotyping, and we will present the results of our progress to date. Overall, our results demonstrate that genome scans are a promising means of identifying candidate regions that have been subject to local selection. 

Single nucleotide polymorphisms have been used to assess the genetic risk of developing a complex disease, particularly by using candidate genes putatively involved in the etiopathogenesis. Coronary Hearth Disease (CHD) is a complex disease with a high prevalence in developed countries. Several polymorphisms have been reported as possible factors of susceptibility in case-control studies. We have compiled a frequency polymorphism database for seven genes (ACE, APOE, MTHFR, PON1, Prothrombin, Factor V and AGT, comprising 6 SNPs and 1 Alu polymorphism) from case-control studies that have been associated to CHD in Europe and North-African populations. We have studied their spatial distribution and the correlation between the SNP allele frequency and  the incidence of the disease. For five of seven polymorphisms we have observed clinal patterns with a North-South direction. A significant negative correlation between the frequency of susceptibility polymorphisms and the incidence of the disease was observed in three of seven biallelic polymorphisms (ACE, MTHFR and Prothrombin) and a positive but not significant correlation was obtained in other three (APOE, Factor V and PON1). No correlation was obtained with AGT. Our results suggest that the geographical distribution of SNP polymorphisms associated with CHD is not quite different than those classicaly considered as neutral and can be related to historicaly migratory processes such as the Neolithic wave of advance. This distribution is also observed in the incidence of the disease, which implies that an elevated number of  genetic polymorphisms are going to show a negative-possitive correlation with the incidence, no matter whether they are realy implicated in the development of the disease or not. The presence of a negative correlation in genes classicaly associated to the disease and differences in the population incidence of the disease can be explained by a predominant role of environmental factors.

I am interested in the analysis of the spatial patterns of gene diversity in genes related to genetic diseases, both mendelian and complex, and their relationship with the history of populations.

Lao O, Andres AM, Mateu E, Bertranpetit J, Calafell F. (2003) Spatial patterns of cystic fibrosis mutation spectra in European populations. Eur J Hum Genet. ;11(5):385-94.
Andres AM, Lao O, Soldevila M, Calafell F, Bertranpetit J.(2003) Dynamics of CAG repeat loci revealed by the analysis of their variability.Hum Mutat. 21(1):61-70
Mateu E, Calafell F, Lao O, Bonne-Tamir B, Kidd JR, Pakstis A, Kidd KK, Bertranpetit J.(2001) Worldwide genetic analysis of the CFTR region.Am J Hum Genet. 68(1):103-17.

To investigate the patterns of diversity and the evolutionary history of Eurasians, we have sequenced a 2.8 kb region on Xp11.23 in a sample of African and Eurasian chromosomes. This region is in a long intron of CLCN5 and is immediately flanked by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE. Compared to Africans, Eurasians showed a marked reduction in sequence diversity. The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole sample. Coalescent simulations including recombination and exponential growth indicate a median length of strong linkage disequilibrium up to ~9kb for this area. This implies that the region sequenced is unlikely to be under the strong influence of selective processes on CLCN5, mutations in which have been associated with disorders like Dent's disease. In contrast, a scenario based on a population bottleneck and exponential growth seems a more likely explanation for the reduced diversity observed in Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches a gene diversity value over 98% in Eurasians) suggest an estimated age of origin of the Euro-Asiatic diversity of compatible with a recent out-of-Africa model of colonization of Eurasia by modern Homo sapiens.

The innate immune system is the first line of defense against invading pathogens and is particularly important in warding off bacterial and viral infections presenting at the mucosal cell surface. Given the position of innate immunity genes and the proteins they encode at the interface of host and environment, variation in these genes could have a major impact on downstream responses that could be critical for host defense against pathogens, and therefore, they may be targets of natural selection.
The human innate immunity DC-SIGN family genes, DC-SIGN and L-SIGN, encode C-type lectins that serve as adhesion receptors and have been shown to bind pathogens, such as Mycobacteria tuberculosis, HIV, Hepatitis C and Dengue virus. The two proteins encoded by these genes share ~80% of amino-acid identity and they have been proved to have functional similarities. We investigated allelic variation in 11 kb of genomic DNA sequence from the DC-SIGN gene region, which is located on chromosome 19p13.2-3 and includes DC-SIGN and L-SIGN, which are separated by only 15.7 kb. Sequence variation was determined in 60 individuals (120 chromosomes) from three major geographic regions: Africa (20), Europe (20) and Asia (20). The average nucleotide diversity, ?, differed both between the two genes and among populations; DC-SIGN nucleotide diversity in Europeans and Asians showed lower values (3-5 times) than those of L-SIGN, while for Africans, ? values were similar for the two genes. Haplotype diversity values were also found to be different between them; DC-SIGN showing lower number of haplotypes than L-SIGN in all populations. The comparison of haplotype trees between DC-SIGN and L-SIGN evinced a contrasting pattern. In the DC-SIGN tree, two clearly separate haplotype-clusters were observed. One cluster, containing a group of closely related haplotypes, was restricted to African populations. This cluster, which is characterized by the concomitant presence of three non-synonymous mutations, differed from all other haplotypes belonging to the other cluster by at least 17 nucleotide positions. The presence of two distinct haplotype clusters in the DC-SIGN tree may be due to population subdivision, which can allow divergent clusters to evolve in different demes. Under these conditions, divergent clusters should be restricted to different geographic areas. Within the African landscape, this is not the case. Both clusters are widespread geographically, although one is present at much higher frequencies (82%) than the other. These observations suggest that demography has not been the sole factor affecting DC-SIGN evolution. Additional evidence for this comes from the topology of the L-SIGN haplotype tree, which is at odds with that of DC-SIGN, where no divergent haplotype clusterers were observed. This observation is surprising in view of close physical distance between the two genes that, under a neutral model, should exhibit similar patterns. In addition, pairwise linkage disequilibrium (LD) measures along the DC-SIGN / L-SIGN region showed non-significant levels of LD between both genes, making a hitchhiking effect between them unlikely. Altogether, the differences in nucleotide diversity and the contrasting topology of the haplotype trees between these two close genes suggest that selection may have had some role in the evolution of these gene family along human history. 

I will describe some initial attempts to make detailed inferences about historical admixture events, based on multi-locus genotype data.When populations with distinct gene frequencies meet, "hybrids" are created. In this situation, we would first like to know which individuals are hybrids and which individuals are pure descendents of the ancestral populations. The program "Structure" (Pritchard et al. 2000) can be used to estimate gene frequencies in pre-admixture populations and estimate the proportion of ancestry of each individual from each population.
The latest published version of Structure (described in Falush et al. 2003a) takes linkage relationships between markers into account by assuming that the population of origin of each marker forms a Markov chain running along the chromosome. This additional information improves the technical quality of the inference. Further, the size of the chromosomal chunks inherited from each population provides information on the timescale of admixture. I will describe (unpublished) attempts to utilize this information to infer properties of the admixture process that are of anthropological interest.
The methods will be illustrated by application to data from African Americans (see Falush et al. 2003a) and Helicobacter pylori (see Falush et al. 2003 a and b). I will relate my work to classical work on gene frequency clines by Cavalli-Sforza and colleagues and in doing so emphasize the explicitely spatial nature of many admixture problems.

Pritchard et al. (2000) Genetics 155:945-59
Falush et al. (2003a) Genetics 164:1567-78
Falush et al. (2003b) Science 299:1582-5

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 623 males from closely spaced locations in Continental Italy and Sardinia for 10 haplogroups (Hg), and their internal microsatellite variation. 
Sardinia stands out as an outlier, due to the prevalence of Hg I1b2[1]. In Continental Italy, heterogeneity is not organized along the lines of clinal variation deduced from studies covering the entire European continent. We explored in detail the instances of local peaks in Hg frequencies. With a few dinucleotide microsatellite loci, it was possible to show that a single STR allele often marks these increases, suggesting a limited number of founders. 
Hg P*(xR1a) consistently shows high frequencies (48-76%) in four locations geographically clustered in Northern Italy. In the remaining locations the frequencies of this Hg fluctuate between 11 and 45%, without any obvious geographical trend. These results are in line with a sharp rather than clinal change, already detected by isozymes and blood groups[2]. We also typed with 7 additional STR the P*(xR1a) chromosomes sampled in the location where this Hg has its peak frequency. In this set we found modal STR haplotypes based on 5 and 7 loci which correspond to the Atlantic Modal Haplotype of Hg1 chromosomes from Central-western Europe[3] and to the European Modal Haplotype in the ystr.org database [4] recently assigned to Hg P*(xR1a) [5], respectively. They constitute 21.4% and 16.7% of the entire sample, rising to 57.1% and 40.5% adding the clusters of their one-step neighbours. Also, the modal YCAII-DYS413 STR haplotype observed in the four Northern Italian locations is identical to that found on 67% of  Basque Hg P*(xR1a) chromosomes[6]. 
These findings reveal the persistence at high frequency, of a pre-agricultural component of the Y gene pool at least in some locations South to the Alps. The extant Y chromosomal genetic picture of Italy is then interpreted as the result of the incomplete colonization of the country by newly arrived lineages (mainly in the South), which replaced or diluted the pre-existing ones.
Work supported by grants PRIN_MURST 2002 to A.N. and MIUR COFIN 2001 to G.P.

[1] Semino et al. (2000) Science 290:1155
[2] Barbujani & Sokal (1990) PNAS 87:1816
[3] Wilson et al. (2001) PNAS 98:5078
[4] Roewer et al. (2001) Forensic Sci. Int. 118:106
[5] Gusmao et al. (2003) Forensic Sci. Int. 134:172
[6] Malaspina et al. (2000) Ann. Hum. Genet 64:395

The present work, devoted to the evolutionary history of the Mediterranean land mollusc Cornu aspersum and concerned with the distribution of the genetic variation between populations, provides the first broad-scale screening of allozyme variation since all populations that have been previously analysed are treated together. The occurrence of viewing a continuous range of populations instead of separate historical entities should indeed improve our understanding of the C. aspersum expansion in Western Mediterranean and provide information on colonization routes used from the centre of origin of the species to the northern part of its distribution area. 
The aim of the analysis was to cluster the 102 samples of C. aspersum into groups following rules of geographical proximity and genetic similarity between populations. This approach, based on the fact that active dispersal more than human transport should have played a significant part in shaping the present day distribution of the genetic variation, is performed by using clustering methods with spatial contiguity constraint. Spatial relationships among samples were represented by a list of connections established by means of the Delaunay triangulation method whilst a k-means approach-based clustering algorithm was used to help defining homogeneous groups. Reassignation tests were used to validate the spatial structuring obtained and the six final homogeneous groups defined were described using inertia criteria. The presence of spatial arrangement in the genetic data and the kind of pattern in case of a significant association between genetic and geographic information were tested by computing Mantel statistics for the whole set of populations and for each group. The performance of k-means procedure was then studied by comparing the inferred genetic structure obtained with other various methods for defining homogeneous groups, i.e. the Monmonnier and the SAMOVA algorithms. 

We genotyped a total of 389 males from Somalia, Sub-Saharan Western Africa, Turkey, and Iraq by a PCR based assay with co-amplification of 25 DNA-fragments and detection of 35 Y chromosome biallelic markers with the single base primer extension technique. A total of 19 different haplogroups were identified. In Somalis, 14 haplogroups were identified. The haplogroup E3b1*(xE3b1b) was found in 77.2 % of the male Somali population, in 6.3 % of Iraqi males and in 1.7 % of male Turks whereas E3b1* was not found in Sub-Saharan Western African males. The frequency of haplogroup E3b1*(xE3b1b) in Somali males is the highest observed in any populations to date, and we suggest that the Somali male population is the origin of this haplogroup. Furthermore, the results are in agreement with a gene flow from Eastern to Northern Africa from a homeland in Somalia. In Somalis, 13.4 % of the males carried J or K haplogroups, which are found relatively frequent in e.g. Iraqis, Turks, and other Arab and Asian populations. This might reflects the historical findings of foreign trading posts at the Somali Gulf of Aden from the 7th century. The distribution of haplogroups will be compared to those in Western African population.

Many societies, often described as "traditional", construct kinship groupings, roles, and relationships by tracing descent exclusively through the male or female line. Patrilineal systems are much more common than matrilineal systems, occurring roughly twice more often. These societies are organized in units that fit into each other: tribes are divided in clans that are themselves divided in lineages. These units are more generally called unilineal descent groups. Each unit claims to have a common ancestor, more or less distant in the past, which differentiate them from the other units of the same level. This claim can only be verified with known genealogies at the lineage level. So the question of the reality of these common ancestors for the higher level groups remains unanswered by classical means.
This study aims at testing the reality of these claimed common ancestors by the use of genetic information. We studied the case of five patrilineal populations living in the Karakalpakia region of Uzbekistan: the Uzbeks, the Kazaks, the Turkmen and two groups of Karakalpaks. They are former pastoral nomads and have recently adopted a semi-nomadic way of life, balancing between agriculture and pastoralism. We gathered ethnological information (membership to descent groups) on a sample of 247 men from these five populations and typed them for several polymorphic markers (SNPs and 13 microsatellites) of the paternally inherited Y chromosome. An ethnological distance was calculated for each pair of men depending on their memberships to identical of different descent groups. At the same time, a genetic kinship coefficient based on the Y chromosome polymorphisms was estimated for each pair of men. Then, the mean genetic kinship coefficient for each ethnological distance class was computed as well as the significance of the correlation between genetic kinship coefficient and ethnological distance. 
The results showed a significant negative correlation between genetic kinship coefficient and ethnological distance. For each of the five populations, the kinship coefficient of men belonging to the same clan or belonging to the same lineage was significantly higher than the mean kinship coefficient in the population, supporting the hypothesis of a common ancestor for people of a same clan or lineage more recent than the ancestor of the population. Consequently, the ancestor they claimed might have really existed. Conversely, the kinship coefficient of people belonging to the same tribe was not significantly different from the mean kinship coefficient in the population. This led us to propose that the common ancestor claimed by people from a same tribe is not real but imagined and socially reconstructed. This is one of the hypotheses suggested by ethnologists. A tribe might be a conglomerate of clans of diverse origins.

The great majority of sub-Saharan Africans speak one of > 500 closely related Bantu languages. The highest linguistic diversity of the Bantu family is found in Nigeria and western Cameroon, suggesting this area as the « core » region of the Bantu dispersals starting 5000 YBP. The Ogooué-Ivindo region, covering Gabon and parts of Congo-Brazzaville, is located in the southern lobe of the putative Bantu homeland and it has been extensively studied from a linguistic standpoint. Central Africa is poorly sampled and mtDNA variation in this region remains largely uncharacterised. We have therefore defined mtDNA variation 308 individuals from 7 Bantu-speaking populations from the Ogooué-Ivindo area in order to (i) determine the maternal variation in central African populations and compare it to the global African landscape and (ii) to contrast the linguistic classification of these populations with genetic data. All individuals, which belong to Fang, Galoa, Mitsogo, Kele, Punu, Obamba and Teke populations, were analysed for HVS-I sequence variation and a number of coding-region sites. Overall, high sequence and lineage diversity values were observed in all populations. The amount of variation due to inter-population diversity turned out to be very low (~1%), indicating that virtually all variation is explained by intra-population diversity. Standard neutrality tests suggested that all populations, except the Galoa, exhibit signals of population growth. The two most prevalent lineages in the Central African populations studied are L1c and L3e. The origin of L1c lineage remains controversial since is found at high frequencies in African-Americans, but in Africa it has been observed in some central and west Africans. It has been suggested that it could have originated in Central Africa, since west African sequences tend to be derived from central African ones. L1c lineage is present at highest frequencies in our populations (20-40%) and therefore, strongly suggests a central African origin for it. The second most prevalent lineage in our samples is L3e. It is present at low frequencies in west and east Africans but it has been found at higher frequencies in a small central African sample and in southeastern populations. Both its distribution and internal diversity suggest a central African origin of L3e that was probably subsequently dispersed into the southeast via the Bantu-expansions. Our data have also shed light on the linguistic classification of the different Bantu-speaking groups of Gabon. Detailed linguistic comparisons have evinced two major linguistic clusters: a northern cluster, comprising the B10 and B30 groups represented by the Galoa and Mitsogo respectively, and a southern cluster, comprising the B40, B60 and B70 groups represented by the Punu, Obamba and Teke respectively. Our genetic data strongly support the linguistic grouping of the northern cluster, while the southern cluster seems to be less supported. The latter observation could be due to long-term linguistic convergence as a result of prolonged contact with few genetic exchanges among these populations. In addition, the origin of the Fang population, who claims a Semitic origin in Egypt and not to be related with their Bantu-speaking neighbours, has been clarified. No detectable traces of an Egyptian origin were observed in this population, who otherwise exhibits strong genetic affinities with neighbouring Bantu-speaking groups, in contrast with Fang cultural tradition. However, Y-chromosome data is needed to conclusively clarify the origins of this population.

In high altitude (HA) residents, haematocrit and haemoglobin level are normally increased to allow for a better adaptation to the ambient decrease of oxygen partial pressure. In some cases, this erythrocytosis is excessive and induces a chronic inadaptation to life in altitude. The primary excessive erythrocytosis can be observed in young men born and permanent residents in HA without previous pathology (Guenard, 1984; Vargas, 1989). The secondary excessive erythrocytosis is also observed in some HA patients suffering from diseases inducing chronic hypoxia such as respiratory and cardiac insufficiency, obesity, thorax deformations, etc. The abnormal increase of red cells can be concomitant with headaches, memory loss, oxyhemoglobin desaturation, progressive dyspnoea, pulmonar arterial hypertension and right ventricule hypertrophy. Excessive erythrocytosis is present in the Aymara population living in La Paz and surroundings at a frequency of about 5 to 15%. (Tufts 1985). 
Analysis of mitochondrial DNA (mtDNA) haplogroups has been performed in the Aymara population living in La Paz or in close by villages at altitudes ranging between 3,600 and 4,000 m.The mtDNA haplotype B was found at a frequency that can reach 80 to 90% of this population. This % was the highest in areas that were the most remote from the city of La Paz and in which the Caucasian admixture was the least important. It ranged from about 70% in the student population of La Paz to about 90% in the Aymara-inhabited village of Ventilla. Observing a similarity between the frequency of non-B haplotype in the Aymara population and the frequency of excessive erythrocytosis in the same population, we made the hypothesis that mtDNA haplotype B might be related to a factor involved in the protection against this disease in the Aymara population living on the Bolivian Altiplano. In agreement with this hypothesis, we observed that mtDNA haplotype B frequency in Bolivian Aymaras residing in the vicinity of 4,000 m of altitude and suffering from excessive erythrocytosis was lower than that observed for normal subjects that did not exhibit excessive erythrocytosis. Therefore, mtDNA haplotype B might be one of the factors involved in the better adaptation to high altitude of the Aymara population.

Both shores of the western part of the Mediterranean Sea have experimented numerous human demographic events that have modelled the extant genetic landscape in the region. Focused on the southern shore, different geographical barriers conditioned the human settlement in North Africa: the Sahara Desert in the South, the Mountains in the interior landscape and the Mediterranean Sea in the North. Therefore, this region is of a particular interest to reveal how the demographic events and the geographic barriers have shaped the genetic landscape of Western Mediterranean populations.
The phylogenetic analysis of the mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already described in Europe and the Middle East. Principal co-ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub-Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. Moreover, a spatial autocorrelogram analysis allows to detect a clinal distribution of the haplogroup L. The population genetic structure revealed by the analysis of molecular variance (AMOVA) demonstrates that SW European populations are highly homogeneous, whereas NW African populations display a more heterogeneous genetic pattern due to an east-west differentiation as a result of gene flow coming from the East. The identification of genetic barriers by a Delaunay network approach reveals a genetic separation between NW Africans and SW Europeans. Nevertheless, the European V and the NW African U6 haplogroups are the traces of the Mediterranean Sea permeability to female migrations, and allowed to determine and quantify the genetic contribution of both shores to the genetic landscape of the geographic area.
The present results agree with the conclusions yielded by other genetic markers such as the Alu insertion polymorphisms or the Y-chromosome markers, although the gene flow detected in the present mtDNA analysis is higher than showed previously, as a result of different sexual migration patterns. The analysis of both gene genealogy and geographic distribution has shown that the Sahara Desert and the Mediterranean Sea have not been strong enough to prevent certain degree of gene flow among already differentiated populations, as they were not barriers to the flow of cultures, languages, and religions.

In genetic research of local human populations in B&H over the past three decades numerous patrilocal populations with increased propagational isolation were identified (Hadziselimovic et al 1981). Comparison between the genetic data sets collected before and after the war (Pojskic et al 2003) proved significant influence of war in Bosnia and Herzegovina (1992-1995) on genetic structures of local human populations. 
MtDNA hipervariable region (HV1 and HV2) diversity of three local human populations in alpine area of B&H was investigated. Molecular diversity indices and genetic structure parameters were calculated for three subdivided populations based on their spatial isolation. Historical and ethnographical records show that investigated populations were isolated in the past. Because of its developed infrastructure and connections with urban area, one of the investigated villages (Dejcici) is the center of refugees’ repatriation after four-year exodus. Present population of this village includes returnees that originate from several other villages in the same mountain area. Populations of the two other villages (Bobovica and Lukomir) were expelled and returned home following the seize of atrocities. Presently, these two populations consist mainly of the elders. Due to pronounced geographic isolation their genetic structure was not affected. The named populations were compared against standard Bosnian population (Harvey et al. 2000). 
Haplotype diversity, intrapopulational and interpopulational nucleotide diversity, net nucleotide diversity and coefficient of nucleotide differentiation were calculated. Relationship of clusters found in the observed populations were illustrated by NJ (neighbor joining) and UPGMA (unweighted pair group method with arithmetic mean) trees based on net nucleotide distance.
The stated analyses indicate expected transition of Dejcici population from subdivided to an “open” urban population as an effect of forced spatial dispersion of human groups in the investigated geographic region. 

Our study has two main objectives: (i) understanding the factors responsible for the evolutionary dynamics of homologous and duplicated microsatellites located on sex chromosomes and (ii) to use this knowledge to infer population genetic diversity. The study model is a family of microsatellites (CAIII) constitutes of different loci on X and Y microsatellites. The species model are human (10 Old World human populations) and non human primates (New and Old World).
Using bioinformatic methods, we showed that these microsatellites are located on segmental duplications near the VCXY genes (~ 2.5 kb).
Using an evolutionary approach, we compared these microsatellite sequences in 13 primate species and  showed that: (i) molecular changes both in the repeats and flanking sequences despite their identical genomic environment, suggesting locus-specific factors (e.g. regional mutation rate) and (ii) a flanking sequence divergence 3 to 4 times lower than expected for non-coding sequences, probably due to the vicinity of the evolutionarily constrained VCXY genes.
Using a population genetic study, we genotyped 10 Old World human populations and analysed a sample of 33 populations adding literature data published by Scozzari et al. 1997. We showed that (i) Y-linked within-population genetic diversity is lower than on the X chromosome, suggesting levels of migration 4 to 5 times higher and/or a population effective size 10 times higher in females than in males and (ii) genetic distances between populations were lower than the ones published, suggesting size constraints on microsatellites. 
We hypothesise that selection acts on sex-linked microsatellites: this is emphasised by (i) the vicinity of VCXY genes, thus preventing between-species divergence and (ii) lower than expected sex-linked genetic distances and underestimation of the female:male ratio migration rate and/or effective size.
Our findings emphasise that a good understanding of the evolutionary history and the genomic environment of microsatellites are essential for elaborating precise demographic and selective scenarios to explain the evolution of  population diversity in a given species.