PubMed HealthSearch

Biomedical subjects

A Langaney

Publications and source records attributed to A Langaney.

At least 19 recordsLinked to original sources

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

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.

B-Lymphocytes

DNA analysis of the immunoglobulin IGHG loci in a Mandenka population from eastern Senegal: correlation with Gm haplotypes and hypotheses for the evolution of the Ig CH region.

This study presents restriction fragment length polymorphism (RFLP) and serological analyses of the immunoglobulin CH loci in a sample of 100 individuals from a Senegalese Mandenka population. The RFLP variability is mostly the result of large DNA insertions or deletions in the non-coding flanking regions of the IGHG genes, and to variable number of tandem repeat-like patterns within their 5'-switch sequences. However, part of the IGHG3 polymorphism also corresponds to a variable number of exons coding for the flexible hinge segment of the IgG3 antibody (the 4-exon and 3-exon forms, and a newly described 2-exon form). This diversity presents relevant associations with Gm haplotypes, suggesting that molecular rearrangements of the G3 hinge are related to the evolution of the Gm polymorphism. Non-significant correlation coefficients are found between Gm haplotypes and A2m alleles in the Mandenka, indicating that these loci may have reached equilibrium through recombination. The effect of recombination on linkage disequilibrium is more generally revealed, across the Ig CH genomic region, by a significant decrease of D' values with increasing physical distances between the loci on the chromosome.

Alleles

Evolutionary correlation between control region sequence and restriction polymorphisms in the mitochondrial genome of a large Senegalese Mandenka sample.

We present here the first comparative analysis at the population level between Restriction Fragment Length Polymorphism (RFLP) and control region sequence polymorphism in a large and homogeneous Senegalese Mandenka sample. Eleven RFLP haplotypes and 60 different sequences are found in 119 individuals, revealing that a very high level of mtDNA diversity can be maintained in a small population. A sequence neighbor-joining tree and an analysis of molecular variance show that sequences associated with a given restriction haplotype are evolutionarily highly correlated: sequencing generally leads to the subtyping of RFLP haplotypes. Evolutionary relationships among RFLP haplotypes inferred from restriction site differences are in good agreement with those inferred from sequence data. A single difference is observed and is likely due to a single restriction homoplasy having occurred in the control region. Selective neutrality tests on both RFLP and sequence data accept the hypotheses of mtDNA neutrality and population equilibrium. The deep coalescence times (exceeding 50,000 yr) of sequences associated with the two most frequent restriction haplotypes confirm that the Niokolo Mandenka population has not passed through a recent bottleneck and that gene flow is maintained among West African populations despite ethnic differences.

Base Sequence

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.

Alleles

High diversity of alpha-globin haplotypes in a Senegalese population, including many previously unreported variants.

RFLP haplotypes at the alpha-globin gene complex have been examined in 190 individuals from the Niokolo Mandenka population of Senegal: haplotypes were assigned unambiguously for 210 chromosomes. The Mandenka share with other African populations a sample size-independent haplotype diversity that is much greater than that in any non-African population: the number of haplotypes observed in the Mandenka is typically twice that seen in the non-African populations sampled to date. Of these haplotypes, 17.3% had not been observed in any previous surveys, and a further 19.1% have previously been reported only in African populations. The haplotype distribution shows clear differences between African and non-African peoples, but this is on the basis of population-specific haplotypes combined with haplotypes common to all. The relationship of the newly reported haplotypes to those previously recorded suggests that several mutation processes, particularly recombination as homologous exchange or gene conversion, have been involved in their production. A computer program based on the expectation-maximization (EM) algorithm was used to obtain maximum-likelihood estimates of haplotype frequencies for the entire data set: good concordance between the unambiguous and EM-derived sets was seen for the overall haplotype frequencies. Some of the low-frequency haplotypes reported by the estimation algorithm differ greatly, in structure, from those haplotypes known to be present in human populations, and they may not represent haplotypes actually present in the sample.

Genetic Variation

New data for AG haplotype frequencies in Caucasoid populations and selective neutrality of the AG polymorphism.

We present the results of AG antigen typings of three Caucasoid population samples: Lebanese, Tunisians, and Finns. AG haplotype frequencies estimated by maximum-likelihood methods are compared with the frequencies observed in 13 world populations previously tested for AG specificities by computing a genetic distance matrix used in a multivariate analysis. A high degree of polymorphism characterizes the three samples, with 10 haplotypes detected in the Lebanese and 11 haplotypes detected in the Tunisians and Finns; high heterozygosity levels are also present in the three populations. The genetic distance analysis shows that the three populations possess a genetic structure intermediate between those observed in sub-Saharan Africans and in Caucasoids from the Near East and India. This tight correspondence between AG differentiation and geography is confirmed by a highly significant correlation coefficient found between genetic and geographic distances computed worldwide, suggesting that an isolation by distance model of evolution applies to the AG system. The Ewens-Watterson test for selective neutrality on all world populations tested for AG specificities also supports the hypothesis that the AG system behaves like a neutral polymorphism. Overall, the AG differentiation pattern appears to be close to the patterns observed for other serological polymorphisms, such as RH, GM, and HLA, whose evolutionary mechanisms are also discussed.

Antigens, Differentiation

[Polymorphism of HLA class I loci HLA-A, -B, -C, in the Mandenka population from eastern Senegal].

A sample of 162 Mandenkalu from Eastern Senegal has been typed for three HLA class I loci: HLA-A, -B and -C. The Mandenka population presents a very high genetic variability with 15 alleles for locus A, 24 alleles for locus B, and at least 8 alleles for locus C. The calculated heterozygosities for the three loci A, B, and C are respectively 0.884, 0.944 and 0.829. The Mandenkalu allelic frequencies are close to that found in other sub-Saharan populations. They show, however, some peculiarities like the occurrence of the Bw 56 allele and the high frequencies of both B5 and B35.

Alleles

HLA-DR polymorphism in a Senegalese Mandenka population: DNA oligotyping and population genetics of DRB1 specificities.

HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1*1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequent specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52b (DRB3*02) represents as much as 80.7% of all DR52 haplotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the Mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes.

Base Sequence

Interethnic genetic differentiation: GM polymorphism in eastern Senegal.

Analysis of GM polymorphism has been performed on 1,806 individuals representing three sympatric ethnic groups--Bedik, Fulani, and Mandenkalu--of eastern Senegal. Haplotype frequencies estimated by maximum likelihood have been used to compute common genetic pools between the three samples and a number of other sub-Saharan African populations. Despite extreme linguistic and sociocultural differentiations and very high levels of endogamy, especially in the Bedik and Niokholo Mandenkalu, the three populations share about 90%-95% of their haplotype frequencies in a system which commonly provides strong genetic differentiations. This supports the view that, despite its importance at a large continental scale level, as it is discussed for a set of populations from many regions of sub-Saharan Africa, sociocultural differentiation usually has little effect on local genetic diversity.

Demography

Origin and differentiation of human mitochondrial DNA.

A recent study of mitochondrial DNA (mtDNA) polymorphism has generated much debate about modern human origins by proposing the existence of an "African Eve" living 200,000 years ago somewhere in Africa. In an attempt to synthesize information concerning human mtDNA genetic polymorphism, all available data on mtDNA RFLP have been gathered. A phylogeny of the mtDNA types found in 10 populations reveals that all types could have issued from a single common ancestral type. The distribution of shared types between continental groups indicates that caucasoid populations could be the closest to an ancestral population from which all other continental groups would have diverged. A partial phylogeny of the types found in five other populations also demonstrates that the myth of an African Eden was based on an incorrect "genealogical tree" of mtDNA types. Two measures of molecular diversity have been computed on all samples on the basis of mtDNA type frequencies, on one hand, and on the basis of the number of polymorphic sites in the samples, on the other. A large discrepancy is found between the two measures except in African populations; this suggests the existence of some differential selective mechanisms. The lapse of time necessary for creating the observed molecular diversity from an ancestral monomorphic population has been calculated and is found generally greater in Oriental and caucasoid populations. Implications concerning human mtDNA evolution are discussed.

DNA, Mitochondrial

Common genetic pools between human populations.

A 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 divergences. 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.

Biological Evolution

Further contribution of common Gm*-Am* haplotypes and Km* alleles in the characterization of the Tunisian population.

The Gm, Am and Km allotypes have been investigated in 405 sera from unrelated students and blood donors coming from the different areas of Tunisia. Thirty Gm and fourty-seven Gm-A2m common phenotypes have been observed. Eleven Gm* and seventeen Gm*-A2m* common haplotypes have been deduced from these phenotypes. The Tunisian population appears as mainly Caucasoid (combined frequency of Caucasoid Gm*-Am* haplotypes in the order of 0.81-0.82) with a relatively important Black contribution in the gene pool (combined frequency of Negroid Gm*-Am* haplotypes of 0.17-0.18) and a very low Oriental participation (0.01-0.02). Our results are compared to those previously reported for two other samples of the Tunisian population, the first from the regions of Mahdia and Sfax and the second from several villages of Berbers, the first inhabitants of Tunisia. Likewise, other comparisons are made with populations from Africa, Europe and Asia, since Tunisians are a mixture of Berbers, invaders and immigrants from different origins.

Female

Genetic study of Tunisian Berbers. I. Gm, Am and Km immunoglobulin allotypes and ABO blood groups.

The Gm, Am and Km immunoglobulin allotypes and ABO blood groups were studied in three groups of Tunisian Berbers . The results showed that the actual Berbers of Tunisia present certain heterogeneity and their ancestors were probably the first inhabitants of North Africa. Indeed, although their Gm-Am haplotypes are mainly Caucasoid, some of them are typically African. The group of Kesra village, the most Caucasoid, shows frequencies of Gm-Am haplotypes very close to those of South European populations, particularly the Spanish, who are probably of the same origin. The gene frequencies of the ABO groups in the three Berber groups were similar to those recorded in European populations with a relatively high frequency of the O genes typical of the Berbers .

ABO Blood-Group System

Frequencies of Gm and Km allotypes in the population of Singapore, Sri Lanka and Punjabis in North India.

Serum samples from Sinhalese subjects, from Punjab and from Singapore have been studied. The Gm phenotypes found are very numerous and we can observe some similarities concerning the Gm gene frequencies between the Singapore Indians with the Indians of North India, and with the Sinhalese. In contrast, Gm gene frequencies found among Chinese and Malays from Singapore are quite different from those found among Indians of Singapore. Our results here are very similar to those obtained in Malaya studies.

China

[Measles and temporary increase in masculine births: coincidence or causality?].

Data from three West-African populations shows significant increase of sex-ratio. In two of them a considerable excess of male births came from conceptions the year following an epidemic of measles. This is limited to the villages affected by this epidemic. These facts seem to be similar to those related to hepatitis and sex-ratio. They suggest similarities between measles virus and surface antigens of Y sperms. This hypothesis could be tested by immunological investigation.

Antigens, Surface

Gm, Am and Km immunoglobulin allotypes of two populations in Tunisia.

Gm, Am and Km allotypes were investigated in two Tunisian populations (236 samples from Mahdia and 142 samples from Sfax). These populations descend from immigrants and, therefore, the results were compared with those obtained in other populations living in the Near East and in North Africa. The subclass heavy chain allotypes G1m, G2m, G3m and A2m are inherited in fixed combinations. There were five main and four minor Gm-Am haplotypes that could be deduced from the phenotypes. This led to the conclusion that the populations studied are Caucasoids with some African admixture (about 10%) and a very low oriental contribution. Furthermore, there were 11 samples which showed 8 uncommon Gm-Am phenotypes. These could be explained by the assumption of five different uncommon Gm-Am haplotypes. Four of these may have arisen by equal crossing over of prevalent haplotypes. The fifth may be the result of unequal crossing over of prevalent haplotypes. The fifth may be the result of unequal crossing over, since it was proven, by family study, that more markers are transmitted together than are present in the prevalent haplotypes.

Female

Comparative study of haemoglobin types of two populations of eastern Senegal--Bedik and Niokholonko.

The haemoglobin types of 1487 of the East Senegal Bedik and Niokholonko populations have been studied. There are significant differences between them, the most likely explanation of which is that the populations are of different origins. The Bedik appear to be the most ancient known settlers in East Senegal: they possess only A and S haemoglobins. The Niolholonko came later, probably from Mali: they have a lower frequency of S genes but AC and AD phenotypes are also encountered among them.

Anemia, Sickle Cell