The FMR1 CGG repeat and linked microsatellite markers in two Basque valleys.

Fragile X syndrome is associated with an unstable CGG repeat sequence in the 5' untranslated region of the first exon of the FMR1 gene. The present study involved the evaluation of factors implicated in CGG repeat stability in a normal sample from two Basque valleys (Markina and Arratia), to discover whether the Basque population shows allelic diversity and to identify factors involved, by using the data in conjunction with previous findings. The study was based on a sample of 204 and 58 X chromosomes from the Markina and Arratia valleys, respectively. The CGG repeat, the AGG interspersion and two flanking microsatellite markers, FRAXAC1 and DXS548, were examined. In the Markina valley, gray zone alleles (> or =35 CGG repeats) were associated with anchoring AGGs, with the longest 3' pure CGG repeats of the valley (=15), with the 5' instability structure 9+n and with one principal fragile X FRAXAC1-DXS548 haplotype 42-50. In the Arratia valley, gray zone alleles (> or =35 CGG repeats) showed the highest frequency among the Basque samples analyzed, and were associated with anchoring AGGs, with the longest 3' pure repeats (> or =20), with the 5' instability structure 9+n and with one "normal" FRAXAC1-DXS548 haplotype 38-40 (these data from Arratia suggest the existence of a "protective" haplotype). The results showed, on the one hand, differences between Markina and Arratia in factors implicated in CGG repeat instability and, on the other hand, a great similarity between the general Basque sample from Biscay and the Markina valley.

In vitro and in vivo evaluation of the antihypertensive drug atenolol in cultured human lymphocytes: effects of long-term therapy.

The genotoxicity of atenolol, a beta-blocker antihypertensive drug, both in vitro and in vivo, was cytogenetically tested for its ability to induce sister chromatid exchange (SCE) and micronuclei (MN) in cultured peripheral lymphocytes. Also, fluorescence in situ hybridization (FISH) with a centromeric probe was performed to determine the origin of the induced MN. The in vivo study was carried out, on the one hand, on four patients under antihypertensive treatment with atenolol and, on the other hand, on four matched control individuals taking an oral dose of atenolol. The in vitro study was performed on the control individuals by adding the drug to the culture medium at a final concentration similar to the levels found in plasma. When a comparison was made, the frequency of SCE did not show significant differences in any case. A statistically significant increase in the frequency of MN was detected in patients but not in control individuals either in vitro or in vivo. FISH analysis revealed statistically significant differences between patients and control individuals without the drug with respect to the frequency of centromeric signals in MN. Taking all these observations together, our data suggest that chronic exposure to atenolol resulted mainly in the induction of chromosome loss, so an aneugenic activity could be predicted. Different sensitivity to the compound was observed among control individuals. Nevertheless, all of them responded to the presence of atenolol in the same way in both assays. Interindividual variability was also reported. The intervariability seen in patients suggested an adaptive response to the chemical after long-term therapy.

A survey of fragile X syndrome in a sample from Spanish Basque country.

Fragile X syndrome is the most common inherited form of mental retardation. The syndrome is associated with a CGG repeat expansion in the 5'UTR of the first exon of the FMR1 gene. This gene maps to Xq27.3 and coincides with the cytogenetic fragile site (FRAXA). The present study deals with the prevalence of fragile X syndrome among individuals with mental retardation of unknown cause from institutions and special schools from the Spanish Basque Country. Results of cytogenetic and molecular studies, performed in a group of 134 unrelated individuals (92 males and 42 females) are presented. The cytogenetic marker at Xq27.3 was identified in 12 patients. Other chromosomal abnormalities were found in two cases that this and previous studies confirmed as Angelman and Prader-Willi syndromes. Two males, in whom the cytogenetic marker was identified, were found negative for FRAXA and FRAXE expansion at the molecular level. The present study shows that the frequency of the FRAXA full mutation in individuals of Spanish non-Basque origin is in the range of other Spanish populations. In the sample of Spanish Basque origin we have not found cytogenetic FRAXA site expression, and the CGG repeat size of FMR1 gene is in the normal range. The significance of these results are discussed.

a-b ridge count in a Basque population: fluctuating asymmetry and comparison with other populations.

We have analyzed the a-b ridge count and its fluctuating asymmetry in a sample (331 males and 290 females) from the Basque region of Alava province, Spain. Significant bimanual differences in the a-b ridge count are apparent only for females, and the sexual differences are significant for both hands. A comparison of the results in the Alava Basque population with results for other Basque populations showed sexual dimorphism. The results for fluctuating asymmetry do not support the hypothesis that if the regression of fluctuating asymmetry on the right and left hands is quadratic, the fluctuating asymmetry is a result of developmental homeostasis. Our data seem to indicate also that the factors that determine the a-b ridge count are canalized in females and males in the same way.

Fluctuating dermatoglyphic asymmetry: genetic and prenatal influences.

Genetic and environmental prenatal factors influencing the fluctuating asymmetry of the a-b interdigital ridge count are examined. From the results obtained we can conclude that fluctuating asymmetry of the a-b interdigital ridge count is poorly influenced by genetic factors. We suggest that fluctuating asymmetry of dermatoglyphics provides a good measure of developmental stability in humans, especially for males. The results also indicate that random environmental factors, acting before the 19th week of embryonic development, could be related to the differential timing of maturation of the sexes.

Genetic and dermatoglyphic distances among Basque Valleys.

Palmar dermatoglyphics of a sample including 552 males and 701 females from 8 Basque valleys were analyzed. We studied the frequency of palmar pattern types and compared them using correspondence the frequency of palmar pattern types and compared them using correspondence analysis. The results of this comparative study show that there is diversity among valleys and also that this diversity depends on the trait and on sex. Genetic drift could explain this variability found in the Basque population.

Effects of genetic and environmental factors on the a-b, b-c and c-d interdigital ridge counts.

A study of 100 MZ (55 female and 45 male) and 97 DZ (50 male and 47 female) same-sexed twin pairs was carried out to analyse the genetic component of the variance of the a-b, b-c and c-d interdigital ridge counts by means of the Christian method. Especially for the a-b interdigital ridge count, we found it important to analyse both sexes separately. Our results suggest that the a-b count in males seems to be more influenced by environmental factors than the other counts. For females, the three interdigital counts seem to have a strong genetic component influencing their phenotypic expression. Factor analysis with VARIMAX rotation showed each interdigital ridge count to be genetically independent.

Are the Basques a single and a unique population?

Different analyses of genetic polymorphisms performed on the Basque population have suggested a possible heterogeneity of the Basques and a singularity of their genetic characteristics. In this paper, both aspects are analyzed by means of the genetic study of seven polymorphic systems--ACP, ADA, AK, ESD, PGD, GC, and HP--in 854 autochthonous individuals from the province of Vizcaya. The individuals were classified as being from the regions of Arratia, Guernica, Durango, Uribe, Marquina, Lea, and Bilbao, on the basis of the birthplaces of their four grandparents. Analyses for heterogeneity of the gene frequencies distribution suggest that there is a moderate genetic heterogeneity, probably produced by centuries of geographical and administrative isolation of these regions. The comparison with caucasoid populations, performed using the principal components analysis and Cavalli-Sforza and Edwards arc distance, indicates that the subpopulations of the province of Vizcaya have experienced little genetic exchange with other caucasoids and that the distribution of their genetic frequencies differentiates them from other populations.

Characterization of digital dermatoglyphic features in Salazar Valley: comparison with other Basque valleys.

Digital dermatoglyphics of a sample from the Basque Valley of Salazar, situated in the West of the Pyrenees, were analysed. The results showed bimanual differences in both sexes, and also sexual differences for both hands. The comparative study with other Basque valleys showed that, in spite of their supposed common origin, the geographic barriers and the isolation have generated a genetic/dermatoglyphic and linguistic differentiation.

Fluctuating asymmetry in quantitative dermatoglyphic traits: twins and singletons.

Fluctuating asymmetry for the digital quantitative value was analyzed in a sample of twins (mono and dizygotic) and singletons. The aim was to check if the influence of twinning on the development is expressed in a higher fluctuating asymmetry in twins than in singletons. The results have shown that significant differences exist among the three groups studied, and these differences are fundamentally expressed when the radial and ulnar counts are considered separately.

Twin study of digital dermatoglyphic traits: Investigation of heritability.

Digital patterns of a sample of monozygotic and dizygotic twins were analyzed to obtain heritability values for the four basic types of patterns: arch, tented arch, loops, and whorls. Loops have been separated according to their orientation radial or ulnar. To carry out this study, we used the Holzinger and Clark indices. The results show highest concordances for monozygotic twins except for ulnar loops of the left hand and radial ones of the right hand. Different values of heritability were found for the right and left hands, with finger I having the highest values.

Analysis of digital patterns in the Basque valley of Deba: multivariate comparison with other populations.

Eighty-six females and 79 males from the Basque valley of Deba were analyzed with respect to their digital patterns using correspondence analysis. We found that there was a significant sexual difference for only one type of pattern, tented arch. Also, this population was compared with other Basque valley populations and with other Spanish populations. We found great variability among Basque subpopulations, despite their supposed common origin. Dermatoglyphic distances for some traits can be interpreted as genetic distances because there is high heritability of these traits. The results of the comparison between the Deba valley population and other Spanish populations showed that the Deba population is markedly distant from the other populations.

Quantitative and qualitative finger dermatoglyphics in the Basque Valley of Urola, Spain.

Digital dermatoglyphics of an indigenous sample of 87 males and 101 females from the Urola Valley in the Spanish Basque Country are compared with those from the nine other Basque valleys previously analyzed. In both sexes of the Urola Valley, there is a very high frequency of radial loops; the mean found in this valley extends the range of variation for South European-Mediterranean populations, and it is in the superior limit of all Caucasian populations. There are bimanual and sex differences in the frequencies of whorls and loops. Contrary to what occurs normally in populations, in the Urola Valley the frequency of whorls is higher in females and the quantitative value of digital patterns is lower in males. The results of this study show the existence of heterogeneity among valleys for digital trait frequencies and for finger ridge count, and this heterogeneity is more marked in females.

Dermatoglyphic analysis of autistic basque children.

We have analyzed the digital and palmar dermatoglyphics in a sample of autistic children from the Basque Country. The results have been compared with those from a control sample having the same characteristics relative to the ethnic region. We found significant differences between the digital dermatoglyphics of autistic boys and control boys. Autistic children have a higher frequency of transitional radial loops and a lower frequency of dicentric whorls; also the total finger ridge count (TFRC) and radial count are lower in autistic individuals. There were no significant differences in the girls. In palmar dermatoglyphics, autistic girls have a lower frequency of radial loops in the hypothenar area, and the value of the "atd" angle is higher than in control girls. These differences were significant. The a-b interdigital ridge count is significantly lower in autistic boys. Autistic children of both sexes have a higher frequency of aberrant palmar creases. The results obtained in the present study do not contradict the hypothesis that genetic factors may be important in autism of unknown cause.

AK1, PGD, GC and HP frequencies in the Basque population: a review.

A random sample from the Basque population has been studied for 4 polymorphic genetic markers. The gene frequencies are AK1*1 = 0.954, PGD*A = 0.991, GC*1 = 0.663, HP*1 = 0.442. The comparison between the data obtained and other existing studies on Basques shows significant differences. The overall data on the Basque population is heterogeneous for the markers investigated, and the comparison with neighbouring non-Basque populations corroborates this heterogenity.

Some red cell enzymes and haptoglobin gene frequencies in two Basque regions and León.

A study was conducted to determine the distribution of phenotypes and gene frequencies of haptoglobin, phosphoglucomutase 1, esterase D, 6-phosphogluconate dehydrogenase and three monomorphic systems SOD, sMDH and NADH DIA I. Results obtained from two Basque regions and León were compared with those from other Spanish populations. Gene frequencies observed in the León sample were similar to those obtained from the other Spanish samples. The Basque samples differed from the other Spanish populations in the gene frequencies of esterase D.

Finger ridge count in Basque populations: univariate and multivariate comparison with other Spanish populations.

We have analysed finger ridge counts in the indigenous Spanish Basque population (841 males and 911 females). Bimanual and sexual variation have proved to be statistically significant. The results in the Basque population were compared with those of other Spanish populations. In the univariate comparison statistically significant differences appear. The means found in the Basque population are the lowest. Our population is situated on the lower part of the variation range of the European populations for whom data are available. In principal component analysis the first two components explain more than 90% of the total variability. The first component is interpreted as a size component, which is usual. The factor scores of the individual samples have proved to be very useful in showing which populations are nearest to the Basque one.

Digital dermatoglyphics in the Basque population: univariate and multivariate comparison with other Spanish populations.

We have analyzed dermatoglyphic finger patterns in a Spanish Basque population (841 males and 911 females). Bimanual and sexual comparisons have been carried out by means of contingency analysis. The results in the Basque population are compared with those of other Spanish populations, based on univariate (chi 2 contingency test and Student's t-test) and multivariate (principal components analyses) statistical methods. Bilateral distribution asymmetry and sexual dimorphism were observed in the Basque sample. The results of the chi 2 test for pattern types in males and females show statistically significant differences between the Basques and other Spanish populations, with the exception of the males from El Bierzo. Comparing populations with regard to the Pattern Intensity Index, the differences observed are much lower; therefore, this confirms what other authors have suggested regarding the limited usefulness of indexes in populational comparisons. In the Caucasian variation range of pattern types, Basques are located in the high part with regard to arches, in the low part with regard to whorls and radial loops, and in an intermediate part in relation to ulnar loops and overall pattern intensity. Results of the multivariate comparisons show which populations are more or less distant from the Basque population and which variables are significant in contributing to these population relationships.