André Langaney

Human Genetic Affinities for Y-Chromosome P49a,f/TaqI Haplotypes Show Strong Correspondence with Linguistics

Numerous population samples from around the world have been tested for Y chromosome-specific p49a,f/TaqI restriction polymorphisms. Here we review the literature as well as unpublished data on Y-chromosome p49a,f/TaqI haplotypes and provide a new nomenclature unifying the notations used by different laboratories. We use this large data set to study worldwide genetic variability of human populations for this paternally transmitted chromosome segment. We observe, for the Y chromosome, an important level of population genetics structure among human populations (FST = .230, P < .001), mainly due to genetic differences among distinct linguistic groups of populations (FCT = .246, P < .001). A multivariate analysis based on genetic distances between populations shows that human population structure inferred from the Y chromosome corresponds broadly to language families (r = .567, P < .001), in agreement with autosomal and mitochondrial data. Times of divergence of linguistic families, estimated from their internal level of genetic differentiation, are fairly concordant with current archaeological and linguistic hypotheses. Variability of the p49a,f/TaqI polymorphic marker is also significantly correlated with the geographic location of the populations (r = .613, P < .001), reflecting the fact that distinct linguistic groups generally also occupy distinct geographic areas. Comparison of Y-chromosome and mtDNA RFLPs in a restricted set of populations shows a globally high level of congruence, but it also allows identification of unequal maternal and paternal contributions to the gene pool of several populations.

Molecular Analysis of the β-Globin Gene Cluster in the Niokholo Mandenka Population Reveals a Recent Origin of the βS Senegal Mutation

A large and ethnically well-defined Mandenka sample from eastern Senegal was analyzed for the polymorphism of the β-globin gene cluster on chromosome 11. Five RFLP sites of the 5′ region were investigated in 193 individuals revealing the presence of 10 different haplotypes. The frequency of the sickle-cell anemia causing mutation (βS) in the Mandenka estimated from this sample is 11.7%. This mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the β-globin gene were sequenced for a subset of 94 chromosomes, showing the presence of four transversions, five transitions, and a composite microsatellite polymorphism. The sequence of 22 βS chromosomes was also identical to the previously defined Senegal haplotype, suggesting that this mutation is very recent. Monte Carlo simulations (allowing for a specific balancing selection model, a logistic growth of the population, and variable initial frequencies of the Senegal haplotype) were used to estimate the age of the βS mutation. Resulting maximum-likelihood estimates are 45–70 generations (1,350–2,100 years) for very different demographic scenarios. Smallest confidence intervals (25–690 generations) are obtained under the hypothesis that the Mandenka population is large (Ne >5,000) and stationary or that it has undergone a rapid demographic expansion to a current size of >5,000 reproducing individuals, which is quite likely in view of the great diversity found on βA chromosomes.

Worldwide distribution of NAT2 diversity: Implications for NAT2 evolutionary history

BackgroundThe N-acetyltransferase 2 (NAT2) gene plays a crucial role in the metabolism of many drugs and xenobiotics. As it represents a likely target of population-specific selection pressures, we fully sequenced the NAT2 coding region in 97 Mandenka individuals from Senegal, and compared these sequences to extant data on other African populations. The Mandenka data were further included in a worldwide dataset composed of 41 published population samples (6,727 individuals) from four continental regions that were adequately genotyped for all common NAT2 variants so as to provide further insights into the worldwide haplotype diversity and population structure at NAT2.ResultsThe sequencing analysis of the NAT2 gene in the Mandenka sample revealed twelve polymorphic sites in the coding exon (two of which are newly identified mutations, C345T and C638T), defining 16 haplotypes. High diversity and no molecular signal of departure from neutrality were observed in this West African sample. On the basis of the worldwide genotyping survey dataset, we found a strong genetic structure differentiating East Asians from both Europeans and sub-Saharan Africans. This pattern could result from region- or population-specific selective pressures acting at this locus, as further suggested in the HapMap data by extremely high values of FST for a few SNPs positions in the NAT2 coding exon (T341C, C481T and A803G) in comparison to the empirical distribution of FST values accross the whole 400-kb region of the NAT gene family.ConclusionPatterns of sequence variation at NAT2 are consistent with selective neutrality in all sub-Saharan African populations investigated, whereas the high level of population differentiation between Europeans and East Asians inferred from SNPs could suggest population-specific selective pressures acting at this locus, probably caused by differences in diet or exposure to other environmental signals.

Shape Variability and Classification of Human Hair: A Worldwide Approach

ABSTRACT Human hair has been commonly classified according to three conventional ethnic human subgroups, that is, African, Asian, and European. Such broad classification hardly accounts for the high complexity of human biological diversity, resulting from both multiple and past or recent mixed origins. The research reported here is intended to develop a more factual and scientific approach based on physical features of human hair. The aim of the study is dual: (1) to define hair types according to specific shape criteria through objective and simple measurements taken on hairs from 1,442 subjects from 18 different countries and (2) to define such hair types without referring to human ethnicity. The driving principle is simple: Because hair can be found in many different human subgroups, defining a straight or a curly hair should provide a more objective approach than a debatable ethnicity-based classification. The proposed method is simple to use and requires the measurement of only three easily accessible descriptors of hair shape: curve diameter (CD), curl index (i), and number of waves (w). This method leads to a worldwide coherent classification of hair in eight well-defined categories. The new hair categories, as described, should be more appropriate and more reliable than conventional standards in cosmetic and forensic sciences. Furthermore, the classification can be useful for testing whether hair shape diversity follows the continuous geographic and historical pattern suggested for human genetic variation or presents major discontinuities between some large human subdivisions, as claimed by earlier classical anthropology.

Genetic Evidence for Complexity in Ethnic Differentiation and History in East Africa

The Afro‐Asiatic and Nilo‐Saharan language families come into contact in Western Ethiopia. Ethnic diversity is particularly high in the South, where the Nilo‐Saharan Nyangatom and the Afro‐Asiatic Daasanach dwell. Despite their linguistic differentiation, both populations rely on a similar agripastoralist mode of subsistence. Analysis of mitochondrial DNA extracted from Nyangatom and Daasanach archival sera revealed high levels of diversity, with most sequences belonging to the L haplogroups, the basal branches of the mitochondrial phylogeny. However, in sharp contrast with other Ethiopian populations, only 5% of the Nyangatom and Daasanach sequences belong to haplogroups M and N. The Nyangatom and Daasanach were found to be significantly differentiated, while each of them displays close affinities with some Tanzanian populations. The strong genetic structure found over East Africa was neither associated with geography nor with language, a result confirmed by the analysis of 6711 HVS‐I sequences of 136 populations mainly from Africa. Processes of migration, language shift and group absorption are documented by linguists and ethnographers for the Nyangatom and Daasanach, thus pointing to the probably transient and plastic nature of these ethnic groups. These processes, associated with periods of isolation, could explain the high diversity and strong genetic structure found in East Africa.

Nuclear DNA polymorphism in a Mandenka population from Senegal: comparison with eight other human populations

A large and ethnically well defined Mandenka sample from Senegal is analysed for 80 nuclear DNA RFLPs, and compared with eight previously studied human populations. A high level of genetic diversity is found in this sample, comparable to that observed in two African Pygmy samples, but lower than that of a European sample. High population variation is observed for most markers. A neutrality test reveals that the markers used in this study can be considered as neutral. A high correlation is found between genetic and geographic distances (r= 0·62), suggesting that geography does also affect long range population genetic relationships and is an important factor behind differentiation among human populations.

Common genetic pools between human populations

SummaryA further inquiry on modern human origins, based on common genetic pool surveys of rigorously selected population samples and highly informative immunological polymorphisms, provides new evidence of an Occidental-Oriental population split as the origin of human gene pool divergencies. The most likely ancestral genetic profile is discussed in the context of the debate raised by preliminary DNA restriction fragment length polymorphism studies, which contradict the conclusions drawn from classical blood group analyses.

The IGHG3 gene shows a structural polymorphism characterized by different hinge lengths: sequence of a new 2-exon hinge gene

Abstract Four of the five human IGHG genes (G1, GP, G2, and G4) display a hinge region consisting of a unique exon. In contrast, IGHG3 exhibits a different structure in which the hinge is constituted by four or, less frequently, three exons. We report here the nucleotide sequence of a new 2-exon hinge G3 gene found in a Mandenka individual from Eastern Senegal. A comparison of this sequence with that of 4-exon and 3-exon hinge G3 genes suggests that the 3-exon and 2-exon hinge forms arose independently by deletion events in a 4-exon hinge gene.

HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.

Allelic diversity at the HLA‐DPB1 locus was determined by PCR‐oligotyping in a sample of 125 healthy Swiss individuals. A total of 17 alleles were detected among which four main alleles (DPB 1*0401, *0201, *0301, *0402) reached a cumulative frequency of 74.8%. HLA‐A and ‐B (by serology) and HLA‐DRB1 (by oligotyping) allelic polymorphisms were analysed also. HLA‐B and HLA‐DRB1 loci were highly polymorphic with 25 and 28 alleles respectively and similar heterozygosity levels of 0.93 and 0.92. These two loci were found to be more polymorphic than expected under neutrality, while lower heterozygosity levels were found for HLA‐A (0.87) and DPB1 (0.81) loci. This paper presents also a global comparison of DPB1 allelic frequencies among 15 populations from four continents. As opposed to the DRB1 locus, overall DPB1 is shown to have a lower level of polymorphism and may be considered as neutral in all tested populations. DPB 1 genetic diversity is correlated significantly with geography also, as found previously for DRB1. Two‐ and four‐locus haplotype frequencies were determined and the significance of their linkage disequilibrium tested by an original non‐parametric method. A significant positive linkage disequilibrium was found for 11 A‐B, 16 B‐DRB1, 7 DRB1‐DPB1 and 3 A‐B‐DRB1‐DPB1 haplotypes. The overall linkage disequilibrium between DRB1 and DPB1 was much lower than expected from the physical distance and lower than for A‐B and B‐DRB1 pairs. The implications of these results for bone marrow transplantation and for the evolution of HLA loci are discussed.

Inferring the impact of linguistic boundaries on population differentiation: application to the Afro-Asiatic-Indo-European case.

We present here a quantitative way to assess the impact of language-family boundaries on population differentiation and to evaluate the homogeneity of the genetic processes along these boundaries. Our estimator (δa) of the impact of the boundary is based on an isolation by distance (IBD) model and measures the added genetic distance between populations located on different sides of the boundary. We compare this statistic with another estimator of group differentiation (FCT) computed under an analysis of variance framework that does not assume any particular spatial structure of the populations. Monte Carlo simulations are used to study the behaviour of these statistics under a two-dimensional stepping-stone model. Simulations show that FCT can suggest the existence of a frontier when populations only differ because of IBD. This spurious behaviour is much less frequent for the δa statistic. However, the large variance associated with the δa statistic, and the fact that it should only be computed in the presence of IBD, may limit the use of this statistic. Overall, the origin and the effect of the boundary is best understood by comparing different statistics and by testing for the presence of IBD on each side of the boundary as well as across the boundary. We illustrate our approach by examining the boundary between Afro-Asiatic and Indo-European populations. These populations are globally genetically differentiated, but the effect of the linguistic boundary on gene flow seems geographically very heterogeneous. This boundary appears to be the result of a secondary contact between two differentiation centres rather than an enhancer of population differentiation.