Distribution of killer-cell immunoglobulin-like receptor (KIR) in Comoros and Southeast France.

Killer-cell immunoglobulin-like receptors (KIRs) expressed by natural killer cells are cell surface molecules able to recognize groups of HLA class I alleles. The number and distribution of KIR genes vary among individuals and populations. The aim of this study is to analyse the KIR gene content in a Comorian population in order to investigate genetic relationships with other populations and to reconstruct past migration events. The Comorian population consisted of 54 unrelated immigrants living in France and a control population consisted of 38 individuals from Southeast France. We investigated the presence or absence of 15 KIR genes, two pseudogenes expressed and non-expressed forms of KIR2DL5 and the two major subtype full-length and deleted forms of KIR2DS4. All individuals were typed positive for the framework genes, i.e. KIR2DL4, KIR3DL2 and KIR3DL3, and the two pseudogenes KIR3DP1 and KIR2DP1. The frequencies of full-length KIR2DS4 (*00101/00102/002) were lower in the French population (F = 29%) than in the Comorian population (F = 72%) (P(c) < 0.05). No significant differences were found for other KIR genes. A total of 11 genotypes were identified in the Southeast French population and 22 genotypes in the Comorian population. The most common genotype (2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3 and 2DS4) accounted for 41% in the Comorian population and 34% in the Southeast French population. Principal component analysis using KIR gene data from 20 populations was performed to determine genetic differences and relations between populations. The Comorian population exhibited closest kinship with Africans and Asians. As KIR gene content is heterogeneous among ethnic groups, it can probably be used to assess the genetic relationships among populations from different geographic areas.

Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis patients from the French Basque Country.

The distribution of HFE mutations was studied in patients from the French Basque Country with hereditary hemochromatosis (HH). The C282Y mutation was underrepresented but H63D seemed to demonstrate the highest prevalence when compared with other European countries. In addition, symptomatic HH was rarer in autochthonous Basques. This profile is interesting to consider in view of population genetics and should be associated with the search for non-HFE mutations.

Is there a 'Basque' profile regarding autosomal recessive deficiencies of coagulation factors?

When excluding haemophilia and von Willebrand disease, coagulation factors deficiencies constitute rare autosomal recessive disorders (<1 in 500,000) of less precisely defined epidemiology. We have reported herein the distribution of these entities in the French Basque Country, a genetic isolate of very old individualization with peculiar biological specificities. The prevalence of these disorders was markedly high, especially, as already shown, factor XI deficiency. This unusual profile needs to be discussed in the view of population genetics.

Distribution of haemophilia in the French Basque country.

Because peculiar profiles for some genetic haematological diseases have been described among Basques, we aimed to investigate the distribution of haemophilia among this specific population. Hence, we retrospectively assessed all the cases of factor (F) VIII and FIX deficiencies seen in the French Basque country during a 16-year period. Data on 41 patients with haemophilia (FVIII or FIX = 25%) were compiled. Incidence and prevalence for the whole population ranged within the classical limits (but with an unusually high A : B ratio) and tended to be slightly lower in autochthonous Basques (P = n.s.). Our data did not support significant differences in the distribution of this disease among French Basques.

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

A Bayesian approach to infer geographical origins of migrants through surnames.

BACKGROUND: Surnames are an easy tool to analyse human genetic structure, mobility and evolution. Few studies use surnames to estimate human migration at different geographical level. PRIMARY OBJECTIVE: Here we propose the application of a Bayesian method to estimate the probability of geographical origin (pgo) of migrants in a given area using surnames. METHOD: This method can be applied with data recordings when they are available for at least two successive periods and in the areas which are the potential sources of emigration. The principle is that the new surnames which are arriving during the second period in the area under investigation can provide information on their geographical origins. The probability of the origin of migrants can easily be estimated iteratively from the frequency of surnames by using the Bayes' theorem. RESULTS: This method is exemplified using civil birth registers at different geographical scales. The pgo of migrants, estimated between two periods (1891-1915 and 1916-1940), (i) from French departments to Paris (ii), from these departments to Tarbes, and (iii) from counties surrounding Tarbes to Tarbes, are mapped and discussed.

Genome screen for asthma and related phenotypes in the French EGEA study.

A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.

Cystic fibrosis mutations: report from the French Registry. The Clinical Centers of the CF.

Data from 2,666 patients with cystic fibrosis (CF) born in France, submitted during the period of 1992-1996 to the French registry for CF, were used to describe the different mutations, their frequency and their regional distribution. A total of 5,332 CF chromosomes have been analyzed, demonstrating 229 different mutations and accounting for 87% of CF genes in the French population. DeltaF508 is the most common mutation at 67.9% of CF mutations, followed by G542X (2.5%), N1303K (2.0%), 1717-1G-->A (1.2%), R553X (0.8%) and G551D (0.7%). The data show a clear geographical variation in the distribution of many of the mutations. Given the geographical heterogeneity of these mutations, carrier screening does not appear to be feasible in most French regions.

Past malaria, thalassemia and woman fertility in southern Italy.

The role of natural selection in maintaining the thalassemia polymorphism is examined in a southern Italy district, in the past affected by malaria endemia. The Haldane's hypothesis that the thalassemia heterozygotes enjoy more protection than the normal homozygotes against the risk of malaria infection, seems to be confirmed by this indirect study at population level. The higher number of children born of the women who lived in the highly endemic villages, where the highest proportion of heterozygotes occurs, supports the hypothesis that the woman fertility contributes to the thalassemia maintenance. The joint effects of the acquired and inherited immunities and of the reproductive compensation are assumed as the mechanisms through which malaria and thalassemia influence fertility.

Differential fertility as a mechanism maintaining balanced polymorphisms in Sardinia.

Women's fertility, gathered from the 1961 Italian population census, and estimates of heterozygote frequencies for thalassemia and G6PD deficiency (Siniscalco et al. 1961, 1966) in 52 Sardinian villages were examined to study at the population level the mechanisms that have maintained the stability of these polymorphisms over long periods. Sardinian villages were classified according to low or high frequency of heterozygotes, and the reproductive behavior of the women living in these areas was analyzed. A high mean number of children per woman and a low percentage of women without children with a high heterozygote frequency was demonstrated. The observed differential fertility and sterility were interpreted as being the result of different numeric ratios within each area between normal homozygous and heterozygous women, who were less and more resistant, respectively, to malarial infection, according to Haldane's theory. The effect of differing degrees of malaria on fertility rates has been demonstrated previously (Zei et al. 1990). To account for the effect of the genetic and epidemiological composition of an area on reproductive behavior, we classified data on women's fertility and sterility by heterozygote frequency level and malarial morbidity level. A combined and direct effect of inherited and acquired immunities on fertility and sterility rates was shown. The level of endemicity in an area may contribute to decreasing or increasing fitness, which is already influenced by the stable balanced polymorphisms.

Analysis of the molecular variance at the phenylalanine hydroxylase (PAH) locus.

The frequencies of the different haplotypes identified at the phenylalanine hydroxylase (PAH) locus were analyzed for both phenylketonuria (PKU) and normal haplotypes of various European, Asiatic, Polynesian and Black American populations. These molecular variants were studied by applying a specific model of multivariate analysis of variance, allowing an estimation of components of variance at different levels of hierarchical subdivisions (intrapopulation, among different geographical groups of populations, and between PKU and normal haplotypes within populations). The results indicate that the PAH polymorphism could be appropriate to study divergence between African, European and Asiatic population groups, but is not sufficient to explain the diversity among European populations. However, the differences in PAH haplotype frequencies between PKU and normal haplotypes are statistically significant over all European populations.