Y-chromosome DNA haplotype 15 in Europe.

Haplotype 15 at 1 Y-chromosome-specific DNA polymorphism (p49/TaqI) was reported in a meta-analysis concerning 2418 males originating from 28 different geographic locations in Western Europe. The highest frequency of haplotype 15 (72.2%) was observed in French Basques, and it was previously deduced that this haplotype is the ancestral haplotype in Europe (Lucotte and Hazout 1996). Percentages of haplotype 15 geographic distribution show another high frequency in northwestern Europeans and a gradient of decreasing frequencies toward southeastern and peripheral countries. These results suggest that frequencies of haplotype 15 of the Y chromosome are useful to study the contribution of pre-Neolithic males to the present-day populations of Europe.

G542X as a probable Phoenician cystic fibrosis mutation.

When analyzed by origin, the frequency of the G542X cystic fibrosis (CF) mutation (the second most common CF mutation in Europe after DF508) varies between population groups in Europe. We show here that the frequency of G542X varies among different towns or regions of origin, being lower in northeastern Europeans than in southwestern Europeans. The G542X mutation mapping that we have defined by a multiple regression of G542X frequencies covers 28 countries (53 geographic points) and is based on data from 50 laboratories. The more elevated values of G542X frequency correspond to ancient sites of occupation by occidental Phoenicians.

Pattern of gradient of apolipoprotein E allele *4 frequencies in western Europe.

The apolipoprotein E gene (APOE) is located on chromosome 19. The three most common APOE alleles account for most of the corresponding peptide chain variations in most human populations. APOE*3 is the most common allele, coding for the product E3; APOE*2 codes for an Arg-158-->Cys substitution (E2), and APOE*4 codes for a Cys-112-->Arg product (E4). We completed a meta-analysis of APOE allele frequencies from 30 geographically defined populations in Europe, including Iceland and Turkey. We performed a weighted multiple regression using normalized geographic coordinates and a fourth-degree polynomial. Next, we constructed maps showing isofrequencies of the *4 allele in Europe. We found a clear north to south decline in *4 allele frequency for continental Western Europe. No such clinal pattern was apparent for the *2 allele frequencies, but for *3 we found an inverse south to north decreasing gradient. Symmetry between the clines of the *4 and *3 alleles is due to a negative correlation coefficient (r = -0.89). We also plotted APOE allele frequencies against latitude; a decreasing cline was evident for *4 frequencies (y = -0.152 + 0.006x, r = 0.904) and an increasing cline was evident for *3 frequencies (y = 1.087 - 0.006x, r = 0.809). Clines for the APOE alleles could be the result of natural selection.

Patterns of meiotic variability of the (CAG)n repeat in the Huntington disease gene.

We have collected 76 parent-offspring (CAG)n values in 60 French Huntington's disease (HD) pedigrees. The analysis of intergenerational alterations in CAG repeat length shows that there is a correlation between repeat instability and parental repeat length. Paternally inherited cases are characterized by a preferential trend towards an increase in range of repeat sizes in offspring of HD patients.

A new approach for interpreting the genetic diversity in space: 'Mobile Site Method'. Application to Gm haplotype distribution of twenty-seven Amerindian tribes from North and Central America.

We present a new approach, called 'Mobile Site Method' (MSM), to the construction of 'genetic similarity maps' more efficient than that described in a preceding paper (Hazout et al. 1991). After building a triangular mesh between the geographical sites, the method consists of moving these locations at each iteration to reduce the overall differences between the geographic and genetic distances. The genetic similarity map, i.e. the final distorted map, allows the interpretation of the genetic diversity of a population set. We have applied this method to the study of Gm immunoglobulin allotypes of twenty-seven Amerindian groups from North and Central America. By a local weighted linear regression, we have reconstituted the distorted contour of America. This representation completes the observations of the sites during the map distortion. In this study, we have defined a large geographical factor in the genetic data (84% of the variability explained), related to a linguistic factor.

A more detailed map of the cystic fibrosis mutation DF508 frequencies in Europe.

When analyzed by origin, the frequency of the DF508 mutation (the main cystic fibrosis mutation) varies between population groups. We show here that the frequency of the DF508 mutation varies among different populations, being higher in northwest Europeans than in southeast European populations. The map we have constructed covers 25 countries; isofrequency curves were calculated using an original method.

Genetic similarity maps and immunoglobulin allotypes of eleven populations from the Pyrenees (France).

The genetic heterogeneity of eleven populations from the Pyrenees (France) based on the polymorphism of the immunoglobulin allotypes is studied by means of a 'genetic similarity map'. The method described here, called 'Mobile Node Method', allows the deformation of a square grid, in which the studied region is represented, by moving the nodes at each step in order to reduce the difference between the geographic and genetic distances. This tool allows the overall quantification of the genetic heterogeneity of a population set and possibly the study of its dynamics. Other maps constructed to complete the interpretation are 'map of moving vectors', 'iso-displacement curves' and 'site displacements'. This study identified an overall genetic homogeneity among the Pyrenean populations and several local genetic heterogeneities in different regions.

The p49/TaqI Y-specific polymorphisms in three groups of Indians.

The TaqI/p49 Y-specific RFLPs were studied in 98 Indians coming from 3 locations in the country. A new allele (G0) and five new haplotypes (XX-XXIV) were found, not present in Caucasians and in Africans. In the genealogy of haplotypes, the new Indian haplotypes appear grouped together, and all Indian haplotypes occupy an intermediate position between Caucasian and African haplotypes.

Y chromosome DNA polymorphisms in two African populations.

Y chromosome-specific DNA polymorphisms were detected using probe p49f after restriction with TaqI enzyme on samples coming from two African populations: Bantus and Pygmies. All the main TaqI alleles at five Y loci already found in Caucasians are also found in these two populations; 12 of the 16 Caucasian haplotypes were found in these two African populations, and two new haplotypes are Pygmy specific. A proposed phylogeny of the various haplotypes that was derived by using the parsimony criterion established that haplotypes XIII and XVIII, respectively the most frequent one and only one present in Pygmies, are probably ancestral.