Significant Differences In Allele Distributions Research Articles

Dopamine D4 receptor gene polymorphisms: relation to ethnicity, no association with schizophrenia and response to clozapine in Israeli subjects

The dopamine D4 receptor (DRD4) is a candidate gene in the search for a genetic etiology of schizophrenia and for pharmacogenetic factors in the response to antipsychotic treatment. Previous work has not found linkage or association of a polymorphism in exon 3 of this gene with diagnosis of schizophrenia or response to clozapine. In this study we examined this association in Israeli schizophrenic subjects treated with clozapine, compared to ethnically matched controls. Another polymorphism of this gene, in exon 1, was also studied. Both polymorphisms showed no association with schizophrenia or treatment response. A significant difference in allelic distribution of DRD4 exon 3 polymorphism was found between Ashkenazi and non-Ashkenazi control subjects.

Genetic variation and evolutionary stability of the FMR1 CGG repeat in six closed human populations.

In an attempt to understand the allelic diversity and mutability of the human FMR1 CGG repeat, we have analyzed the AGG substructure of this locus within six genetically-closed populations (Mbuti pygmy, Baka pygmy, R. surui, Karitiana, Mayan, and Hutterite). Most alleles (61/92 or 66%) possessed two AGG interspersions occurring with a periodicity of one AGG every nine or ten CGG repeats, indicating that this pattern is highly conserved in all human populations. significant differences in allele distribution were observed among the populations for rare variants possessing fewer or more AGG interruptions than the canonical FMR1 CGG repeat sequence. Comparisons of expected heterozygosity of the FMR1 CGG repeat locus with 30 other microsatellite loci, demonstrated remarkably similar levels of polymorphism within each population, suggesting that most FMR1 CGG repeat alleles mutate at rates indistinguishable from other microsatellite loci. A single allele (1 out of 92) was identified with a large uninterrupted tract of pure repeats (42 pure CGG triplets). Retrospective pedigree analysis indicated that this allele had been transmitted unstably. Although such alleles mutate rapidly and likely represent evolving premutations, our analysis suggests that in spite of the estimated frequency of their occurrence, these unstable alleles do not significantly alter the expected heterozygosity of the FMR1 CGG repeat in the human population.

Apolipoprotein B 3' hypervariable repeat genotype: association with plasma lipid concentration, coronary artery disease, and other restriction fragment polymorphisms

Apolipoprotein B gene 3' variable number tandem repeat (VNTR) and related regions were amplified by PCR and analyzed by agarose gel electrophoresis. Eighteen VNTR alleles (VNTR25, 26, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 58, 60) and 45 genotypes were observed in 477 Taiwanese subjects. The VNTR35 allele and genotype VNTR35/35 were observed most frequently in this population. The polymorphism information content was 0.62. Some minor alleles, such as VNTR25 and 60, were found only in coronary artery disease (CAD) and stroke patients in our sampling, and no statistically significant difference was observed in VNTR allelic frequency between control and CAD or stroke patients. Significant differences in allelic distribution of some VNTR alleles were observed between our normal Taiwanese population and a Caucasian group studied by others. VNTR43-47 and AluI+ (coding Ala591) restriction fragment length polymorphism (RFLP) as well as VNTR49-60 and EcoRI- (coding Lys4154) RFLP were found to be highly coinherited. No apparent association between the VNTR genotype and plasma lipid concentration was observed; however, for the same genotype, the CAD and stroke patients frequently showed higher lipoprotein(a) and lower HDL cholesterol concentrations than the control group.

Genetic variation in the neritic squid Loligo forbesi (Myopsida: Loliginidae) in the northeast Atlantic Ocean

Horizontal starch gel electrophoresis was employed to investigate levels of genetic differentiation between 13 samples of the neritic squid species Loligo forbesi Steenstrup obtained from throughout the majority of its known geographical range. Six enzyme loci identified in a preliminary study as being polymorphic were screened for variation between samples. No significant differences in allele distribution were detected between any of the samples obtained from the Faroe Bank in the north to Lisbon in the south, suggesting that squid throughout this range in the vicinity of the continental shelf are able to maintain panmixia, and effectively belong to a single population sharing a common gene pool. No clinal variation in allele distribution was detected throughout this range, a result which complements the findings of a detailed morphological companion study of the same individuals. Comparison of this homogenous European continental shelf population with squid from the Azores revealed highly significant (P<0.01) differences in allele distribution at five of the six polymorphic enzyme loci studied. A genetic identity value (I) equivalent to 0.93 over 33 loci was obtained. Analysis of F-statistics suggested migration rates between sites to be as low as one individual per five generations, a rate deemed insufficient under most models to prevent divergence by random genetic drift. The large distance and oceanic depths separating the Azores from continental Europe seem to present an effective barrier to gene flow to L. forbesi, a squid belonging to a family considered to be confined in distribution to relatively shallow, near coastal waters. The two populations of squid in the Azores and along the European continental shelf currently both ascribed to L. forbesi should therefore probably best be regarded as relative subspecies.

Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease

Proteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92-kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0.68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10.45 and 20.29 were observed with markers spanning chromosome region 20q11.2-q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.

Genetic evidence of population heterogeneity and cryptic speciation in the ommastrephid squid Martialia hyadesi from the Patagonian Shelf and Antarctic Polar Frontal Zone

Horizontal starch gel electrophoresis was used to investigate levels of genetic differentiation between four samples of the nominate squid species Martialia hyadesi Rochbrune and Mabille, 1889, obtained from regions of the Patagonian Shelf and Antarctic Polar Fron-tal Zone over 1000 km apart. M. hyadesi is an ecologically important South Atlantic ommastrephid squid and it is probable that, in the future, fishing effort will be increasingly directed towards this species. Details regarding the population structure of the species are therefore required. In comparison with the other three samples of M. hyadesi, one of the samples from the Patagonian Shelf (PAT 89II) exhibited fixed allelic differences at 16 of the 39 enzyme loci which were resolved (genetic identity, I=0.51). This high level of genetic differentiation contradicts the apparent morphological similarity between samples, indicating the presence of a cryptic or sibling congeneric species. Deviations from Hardy-Weinberg equilibrium and significant differences in allele distribution were also detected within and between the other three putative M. hyadesi samples, suggesting that the species fails to maintain effective panmixia across its geographical range. The occurrence of both temporal (1986 cf. 1989) and geographic structuring within the species complex is consequently indicated, caused possibly by an overlap of reproductively isolated stocks (stock mixing) outside their respective breeding areas. Low levels of genetic variability were detected throughout the samples examined, estimates of average heterozygosity per locus within the two species detected being in the order of 0.01 and 0.002. These values are discussed in relation to levels of genetic variability reported for other squid species, and in comparison with values typically expected for marine invertebrates.

The genetic structure of the Kuwaiti population. I. Distribution of 17 markers with genetic distance analysis.

Frequency estimates were determined on seventeen blood group, serum protein, and red-cell enzyme markers on random samples of 193 individuals from two Bedouin tribes in addition to the general population in Kuwait. Genetic heterogeneity between the three communities is evident from the significant differences in allelic distribution of the polymorphic markers. Genetic distance measurements were used to compare the results with the oral history of descent of the two tribal communities. Results were in agreement with tribal history.