Association Between the Interleukin-17 Gene Polymorphism -197G>A and the Risk of Prostate Cancer in a Galician Population.

A case-control study was carried out in which the role of the Single Nucleotide Polymorphism rs2275913 in the pathogenesis of prostate cancer was analysed for the first time. This polymorphism is located in -197 position of IL-17A gene and implies a A>G change. The sample consists of 433 Galician men, 241 of whom are prostate cancer patients and 192 are healthy men with no tumours. Besides the influence of this marker, directly involved in the inflammatory process, other variables that were described as prostate cancer risk factors were also studied: age, smoking and Body Mass Index (BMI). By the analysis of Odds Ratio (OR) (CI 95%) a protective effect of heterozygous genotype AG was observed in comparison with homozygous genotypes AA and GG. As regards other risk factors, a significant increased risk was observed in smokers homozygous between 10 and 32 pack-years (p = 0.032). Age and BMI show interesting patterns, but not significant ones. This study shows a possible link between the rs2275913 and the onset of PCa which could be influenced by age, BMI and above all, smoking.

Association of CASP3 genetic polymorphisms rs1049216, rs2705897 and rs4647603 with the risk of prostate cancer in Galicia (NW Spain).

Malfunction of apoptosis plays a key role in carcinogenesis. Previous studies have reported that polymorphisms in caspase genes could lead to poor apoptotic signaling, thus facilitating the onset of several human cancers. The aim of this study was to evaluate the association between three polymorphisms (rs1049216, rs2705897 and rs4647603) of the CASP3 gene and the risk of prostate cancer (PCa) in Galicia (NW Spain).The relationship between these single nucleotide polymorphisms (SNPs) and PCa in European populations has yet to be studied. To test this hypothesis, we carried out a case-control study on a total of 243 patients with PCa and 191 healthy individuals, genotyping all polymorphisms using the matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) method. Overall, none of the polymorphisms were clearly associated with the risk of PCa. Nevertheless, the results drawn from this study suggest that genetic variability in the CASP3 gene, in combination with lifestyle and environmental factors may influence the predisposition to develop PCa in the Galician population. Specifically, the results of study seem to hint at a higher risk of PCa in smokers of up to 20 pack-years (PY) and carriers of both the CASP3-rs1049216 GG genotype and the G allele (OR = 3.61, p = 0.044; OR = 1.71; p = 0.018). In addition, the GG and AG genotypes showed increased predisposition to PCa in overweight individuals (OR = 4.43, p = 0.040; OR = 2.00; p = 0.022). Finally, the CASP3-rs4647603 CT genotype and T allele were associated with a higher susceptibility to PCa in obese individuals (ORCT/TT = 4.30, p = 0.003; ORT/C = 3.58, p = 0.004). Further replication studies in other populations are required to assess these findings.

Allele distribution of 15 PCR-based loci in the Rwanda Tutsi population by multiplex amplification and capillary electrophoresis.

A genetic study of 15 autosomal STRs is carried out (D2S1338, D3S1358, D5S818, D7S820, D8S1 79, D13S317, D16S359, D18S51, D19S433, D21S11, CSF1PO, FGA, TPOX, THO1, VWA) in a sample of unrelated Tutsis. The molecular phenotypes were determined by means of multiplex strategies (AmpFlSTR Identifiler PCR Amplification Kit, Applied Biosystems) followed by capillary electrophoresis.

The Levant versus the Horn of Africa: evidence for bidirectional corridors of human migrations.

Paleoanthropological evidence indicates that both the Levantine corridor and the Horn of Africa served, repeatedly, as migratory corridors between Africa and Eurasia. We have begun investigating the roles of these passageways in bidirectional migrations of anatomically modern humans, by analyzing 45 informative biallelic markers as well as 10 microsatellite loci on the nonrecombining region of the Y chromosome (NRY) in 121 and 147 extant males from Oman and northern Egypt, respectively. The present study uncovers three important points concerning these demic movements: (1) The E3b1-M78 and E3b3-M123 lineages, as well as the R1*-M173 lineages, mark gene flow between Egypt and the Levant during the Upper Paleolithic and Mesolithic. (2) In contrast, the Horn of Africa appears to be of minor importance in the human migratory movements between Africa and Eurasia represented by these chromosomes, an observation based on the frequency distributions of E3b*-M35 (no known downstream mutations) and M173. (3) The areal diffusion patterns of G-M201, J-12f2, the derivative M173 haplogroups, and M2 suggest more recent genetic associations between the Middle East and Africa, involving the Levantine corridor and/or Arab slave routes. Affinities to African groups were also evaluated by determining the NRY haplogroup composition in 434 samples from seven sub-Saharan African populations. Oman and Egypt's NRY frequency distributions appear to be much more similar to those of the Middle East than to any sub-Saharan African population, suggesting a much larger Eurasian genetic component. Finally, the overall phylogeographic profile reveals several clinal patterns and genetic partitions that may indicate source, direction, and relative timing of different waves of dispersals and expansions involving these nine populations.

DYS19 and DYS390 Y-STR polymorphism in the Iberian Peninsula: a multivariate analysis.

Genetic polymorphism of two Y-specific short tandem repeats (DYS19 and DYS390) was investigated in six populations from the Iberian Peninsula (Andalusia, Castilla-La Mancha, Castilla-Leon, Extremadura, Galicia and South East Spain) comprising a total of 895 unrelated and native individuals, and a complete database of DYS19 and DYS390 allele frequency distributions in 34 world-wide populations collected from literature was analysed. DYS19 and DYS390 polymorphism was screened by automated fluorescence analysis of PCR-amplified labelled sample fragments performed with and ABI PRISM 377 Genetic Analyser. The degree of population differentiation was analysed using the STP Test to calculate G Statistic values. Correspondence Analysis based on the allelic frequencies of each locus and combining both was performed using the NTSYS-PC version 1.70 computer package. The diversity of the genetic profiles of gene frequencies suggests an important population heterogeneity in the Iberian Peninsula as a whole (DYS390 being particularly evident), which is corroborated after statistical analyses (G = 139.8457, p = 1.7822 x 10(-14) for DYS19, G = 116.0293, p = 4.6845 x 10(-12) for DYS390). However, multivariate analysis indicates a well defined cluster of the populations of the Central region, and sets them apart from the positions within which peripheral Iberian Peninsula populations are distributed. The Galician population shows trends which bring it closer to the positions throughout which European Atlantic populations are distributed. The results shown by the Central Iberian Peninsula seem to lend support to a model of settlement population stocks which came from the region of Castilla-Leon after the Islam invasions, whereas in the South-East populations the genetic record of Middle Eastern populations is still present, a consequence of the expansion of Islam in Southern Europe in the Middle Ages.

Molecular phenotyping of a trinucleotide repeat (D5S373) experimental conditions.

The aim of this study is to assess the utility of the STR D5S373 in human identification. PCR amplification and electrophoretic separation were optimized in order to achieve unambiguous phenotyping. We concluded that primer concentration and annealing temperature are the main factors affecting the specificity of PCR. In our population survey including three human major groups (Europe, Sub-Saharan Africa, and Asia), up to six alleles and six interalleles have been found ranging in size from 86 to 101 bp. The phenotypes were determined using horizontal polyacrylamide gel electrophoresis, a technique which has turned out to be suitable for separating fragments as close as 1 bp. In each population, the genotype frequencies conformed to the expectations of genetic equilibrium. Sequence studies were carried out to make the allele nomenclature fit to ISFH recommendations. Results from our population analysis of D5S373 show clear differences in allelic frequency patterns among the three major human groups examined. Human identification parameters estimated from our study are similar to those obtained for other STRs currently used in DNA testing.

New STR at the D5S373 locus and its relevance in human population studies.

The genetic analysis of a new trinucleotide repeat (D5S373) was carried out with a view to its application in both individual genetic profiling and human population genetics. In a screening analysis from seven world populations (n = 706) and after nucleotide sequence analysis, up to nine alleles were found corresponding to 8-13 repetitions of a TAA motif. This analysis shows He values ranging between 0.689-0.762. D5S373 reveals interpopulational variability which leads to specific frequency profiles in the major human groups, with alleles 8, 11, l2, and 13 being particularly informative, which suggests the that this marker may be of interest in the biological study of human populations.

Sub-Saharan genetic contribution in Morocco: microsatellite DNA analysis.

Northwest African populations occupy a strategic geographical area that has always been a zone of influence for diverse human groups from different regions. This article focuses on the analysis of the genetic contribution of sub-Saharan African populations by means of four short tandem repeat (STR) systems (HUMTPOX, HUMVWA31/A, HUMTHO1, and HUMF13B), which have proven informative in establishing genetic relationships between human populations. Genetic trees and multivariate analyses of European and Near Eastern populations show that the Moroccan population shares a common genetic substrate with all of them. However, the latter defines a specific lineage. Evolutionary factors inherent in the population's geographical isolation in early times, together with genetic flow from sub-Saharan populations (mainly as reflected by HUMF13B and HUMTPOX), appear to be particularly relevant in understanding the peculiarities of the genetic character of the present-day population.

Study of the ApoB 3' HVR in Galicia (NW Spain). An interpopulational analysis.

The genetic polymorphism of ApoB 3' HVR was analyzed in 200 unrelated individuals from Galicia, North-West Spain, using the polymerase chain reaction followed by horizontal electrophoresis in polyacrylamide gels and silver staining. Up to 17 alleles were detected in this way and a heterozygosity index of 77% was obtained. Significant deviations from Hardy-Weinberg equilibrium were detected using the conventional Pearson's chi 2, while the application of an exact test did not bring about significant values. A Correspondence Analysis among world populations resulted in clustering of the human major groups, although the lack of group specific alleles and the limited discrimination power found among Caucasian populations limit the usefulness of this locus in population genetic studies to some extent, despite its high degree of genetic variability.

Population database of STRs in west Africa: a genetic study of TPOX, HUMVWA31/A, HUMTH01, and CYP19.

Four tetrameric STRs (TPOX, HUMVWA31/A, HUMTH01, and CYP19) were analysed in a West African population (Cabo Verde). No significant deviations from Hardy-Weinberg proportions were observed, either in conventional or exact tests. Pairwise comparisons confirmed allelic independence for all the combinations of loci. Data is provided for the first time about CYP19 in Black populations. In comparisons between African and Afro-American populations, significant frequency differences for several alleles at the TH01 and VWA31/A loci were observed. The allele frequencies provided in this study contribute to a better knowledge of the variability of these markers among the main human groups, especially in the context of Subsaharan African populations.

Further genetic variability of the VNTR D1S80 (pMCT118): Correspondence analysis studies.

A population genetic study of the VNTR D1S80 (pMCT118 locus) in 206 individuals from the Galician population in Spain was carried out. PCR amplified DNA were electrophoresed in horizontal polyacrylamide gels and subsequently were visualized by silver staining. Up to 19 alleles in 56 different genotypes were found. This report describes a new allele tentatively named T11 that defines the lower limit of repeats reported for this VNTR. A family study demonstrates autosomal codominant inheritance of this allele. Levels of heterozygosity indexes are about 80%. No significant deviations from Hardy-Weinberg equilibrium were observed, using the allele binning method (P > 0.3 in all cases). Correspondence analysis shows the usefulness of D1S80 alleles in the genetic profiling of human populations, with the alleles 16, 17, 21, 29, and 31 being of particular interest at different levels of analysis. © 1996 Wiley-Liss, Inc.

Application of two STRs (VWA and TPO) to human population profiling: survey in Galicia.

We have studied two tetranucleotide short tandem repeats (STRs) (VWA and human TPO) in 260 individuals from Galicia by means of polymerase chain reaction amplification followed by electrophoresis separation and silver staining. The feasibility of the analytical technique and the level of polymorphism attained by both systems (PIC = 0.764 for VWA; PIC = 0.563 for TPO) allow us to consider the two STRs as suitable and informative markers in routine population profiling studies.

Distribution of ITI phenotypes in the Iberian Peninsula: Negative correlation between ITI*3 frequencies and latitude in human populations.

The molecular phenotypes of ITI were analysed in samples from seven populations of the Iberian Peninsula (Galicia, Central Portugal, Castilla-Leon, Castilla-La Mancha, Extremadura, Western Andalusia, and Eastern Andalusia) by means of IEF in ultrathin layer polyacrylamide gels followed by immunofixation-silver staining. The observed ITI*3 frequencies exhibit the highest values thus far reported in European populations. Regression analysis between ITI*3 frequencies and latitude reveals a negative correlation (r = -0.8798, P < 0.001). © 1994 Wiley-Liss, Inc.

An alternative modality for the immunodetection of the molecular phenotypes of coagulation factor XIIIB.

A new technical modality for the typing of coagulation factor XIIIB (F13B) is described. The determination of F13B phenotypes was carried out from desyalized plasma samples by means of polyacrylamide gel isoelectric focusing (pH range 6-8) followed by immunofixation-silver stain. This method combines high sensitivity, low expenditure, and a single methodology. A genetic analysis on F13B phenotypes in the Galician population is also discussed.

Alpha-2-HS-glycoprotein gene frequencies in Galicia: further evidence for a cline in European populations.

alpha 2-HS-glycoprotein (AHSG) phenotypes were determined in 506 unrelated autochthonous individuals from the Galician population (NW Spain) by means of isoelectric focusing followed by silver stain immunofixation. The phenotype frequency distribution fitted with the Hardy-Weinberg law. No evidence of intrapopulation heterogeneity was observed. The allele frequencies obtained were: AHSG*1 = 0.7559 +/- 0.013 and AHSG*2 = 0.2441 +/- 0.013. Our findings lend support to the hypothesis of an AHSG gene frequency cline in European populations. Other population genetics' considerations have also been discussed.

Formal and population genetic studies of AHSG: further data from Galicia.

A sensitive immunodetection method for Alpha-2-HS glycoprotein (AHSG) after ultrathin layer polyacrylamide gel isoelectric focusing has been applied to a family study of 126 matings including 292 offspring. Formal genetic studies are in agreement with an autosomal mode of inheritance for this system. A population study of 506 unrelated individuals from Galicia (NW Spain) gave the following frequencies: AHSG*1 = 0.7559 and AHSG*2 = 0.2441, which correspond to a exclusion chance for non-fathers of 0.1505.

Genetic heterogeneity of delta-aminolevulinate dehydrase and phosphoglycolate phosphatase in north-west Spain.

The distribution of delta-aminolevulinate dehydrase and phosphoglycolate phosphatase phenotypes was analyzed in 500 autochthonous individuals from the Galician population (north-west Spain). The gene frequencies for PGP2 and ALADH2 obtained in Galicia have proved to be the lowest of all the European populations so far examined. Comparisons with other world populations were also made.

Genetic heterogeneity of alpha-1-antitrypsin in the Galician population.

Alpha-1-antitrypsin phenotypes were determined in a sample of 496 individuals from Galicia (Northwest Spain) using isoelectric focusing in polyacrylamide gel slabs. Although PMi is the most frequently occurring allele the Galicians are having one of the highest PSi frequencies so far recorded. An allelocline for the distribution of the PSi allele within Europe is discussed. Statistical comparisons with other populations are also made.

Additional data on PGP genetic transmission in family groups.

PGP (phosphoglycolate phosphatase, EC 3.1.3.18.) gentic studies were performed in 188 families including a total of 415 offspring in the Galician population. The results are in agreement with the formal hypothesis of three codominant alleles at an autosomal locus. No silent alleles have been observed.